WO1999053930A1 - Synthetic glycoamines and methods for their use, alone or in combination with other therapies, that affect cell adhesion, inhibit cancer cell growth and metastasis, and induce apoptosis - Google Patents

Abstract

A class of molecules and methods that alter cell adhesion, inhibit growth of cancer cells and metastasis, and induce apoptosis both alone and in combination with standard cancer therapies is disclosed. A method according to the present invention comprises bringing cells into contact with compounds that comprise an amine linked to a carbohydrate wherein the amine and the carbohydrate are linked to form a compound chosen from the group consisting of Schiff bases, N-glycosides, esters, and Amadori products. The carbohydrate is preferably a monosaccharide or a small oligosaccharide. The carbohydrate and amine sub-units may be chemically modified. The carbohydrate sub-unit is preferably a pentose such as arabinose, xylose, ribose, ribulose, a hexose such as fructose, deoxyfructose, galactose, glucose, mannose, tagatose, rhamnose, or a disaccharide based on two of the above such as maltose, lactose, maltulose, or lactulose. A method according to the present invention further comprises bringing cells into contact with the compounds described above before, during, or after administration of another cancer therapy.

Description

1

SYNTHETIC GLYCOAMINES AND METHODS FOR THEIR USE, ALONE OR IN COMBINATION WITH OTHER THERAPIES, THAT AFFECT CELL ADHESION, INHIBIT CANCER CELL GROWTH AND METASTASIS, AND

INDUCE APOPTOSIS

RELATED APPLICATION

This application is a continuation-in-part of U.S. Ser. No. 09/064,568, filed April 22, 1998, which is a continuation-in-part of U.S. Ser. No. 08/758,048, filed November 27, 1996, which is a continuation-in-part of U.S. Ser. No. 08/273,506 filed July 11, 1994, now issued Patent No. 5,629,412. The prior applications were filed by the inventor named herein and are incorporated herein by reference.

GOVERNMENT LICENSE RIGHTS The U.S. Government has a paid-up license in this invention and the right in limited circumstances to require the patent owner to license others on reasonable terms as provided for by the terms of 1R43 CA72284-01A1, Synthetic Inducers of Apoptosis in Metastatic Cells, awarded by National Institutes of Health, National Cancer Institute.

BACKGROUND OF THE INVENTION Various methods of arresting or inhibiting the spread of cancer in patients have been targeted in the search for a cure for the disease. The methods have included attempts to stop the growth of cancer cells, kill or induce apoptosis in cancer cells, or alter a property specific to cancer cells in order to interfere with a mechanism of the spread of cells. One property of cancer cells that is thought to be necessary for the spread of cells throughout the body is a specific degree of cell adhesion. Researchers have had limited success with each of these methods, although often with unwanted side affects.

Stopping the growth of cancer cells has the obvious benefit of limiting the number of cancer cells and hopefully the effect of the cancer cells on the health of the individual. Clonogenic growth potential is considered an important biological property of cancer cells closely associated with malignant transformation and tumorigenicity (Smets, 1989). Clonogenic growth assays are used for a variety of 2 investigations into the growth potential as well as hormone and drug sensitivity of malignant tumors (Von Hoff, et al., 1983; Nomura, et al., 1990).

Killing cancer cells is of course the ultimate goal of any cancer therapy. Apoptosis is programmed cell death as signaled by the nuclei in normally functioning human and animal cells when age or state of cell health and condition dictates. However, cancer cells do not experience normal cell death by apoptosis. Current cancer therapies, such as chemotherapy and γ- and X-irradiation treatment, treat cancer by inducing apoptosis in cancer cells. Barry, et al, 1990; Eastman, 1990; Fisher, 1994; Hickman, 1992; Stewart, 1994). Cisplatin (CDDP, cis- diamminedichloroplatmum), a potent anticancer compound that has improved the treatment outcome of many cancer patients, functions through interstrand DNA crosslinks and the induction of apoptosis (Cress and Dalton, 1996). The taxane class of antineoplastic drugs, particularly Taxol (paclitaxel), have become important in therapy of various cancers such as breast and ovarian carcinomas (Rowinsky and Donehower, 1995; McGuire, et al., 1989; 1996). Taxol functions by enhancing tubulin polymerization and stabilization of microtubules, consequently inhibiting mitosis and inducing apoptosis in target cells (Rowinsky, et al., 1990; Arnal and Wade, 1995; Frankel, et al., 1997). Doxorubicin (adriamycin) and the closely related anthracycline anticancer antibiotic, daunorubicin, induces cellular DNA lesions, formation of DNA adducts and cell death (Cutts, et al, 1991). Similarly to the mechanisms of apoptosis induced by ionizing radiation (Haimovitz-Friedman, et al., 1994), the anthracycline antibiotics act also on the cellular membrane, causing the generation of ceramide and induction of apoptosis (Bose, et al, 1995). These cancer therapies are toxic also to normal cells. Thus, doses must be carefully regulated. Therefore, other methods of inducing apoptosis as well as methods for increasing the efficacy of existing cancer therapies without increasing toxicity are needed.

Cell adhesion is one important property that differentiates multi- cellular organisms from simpler organisms such as bacteria. Cell adhesion is essential to the organization of higher organisms. Without cell adhesion, the organization of cells into tissues and tissues into organs would be clearly impossible. Likewise, the functioning of the immune system also is dependent on cell adhesion. Just as normal 3 cell adhesion is essential to the normal functioning of higher organisms, abnormal cell adhesion is associated with a number of disease states such as inflammation and cancer.

One manner in which cancer cells differ from normal tissue is in their cell adhesion and aggregation properties. Cell adhesiveness is one of the key cell surface-mediated properties that is altered during malignant transformation leading to metastatic dissemination of cancer cells. Metastasis is one of the most important malignant features of human cancer and represents the morphological stage of the generalization of the disease through the body of the tumor host. The abnormal adhesiveness of tumor cells is thought to contribute to the metastatic behavior of these cells. Implicit in the concept of metastasis is the separation of individual cells or small groups of cells from the primary tumor. It has been suggested that the intrinsically low adhesiveness of cancer cells contributes to separation. In particular, tumor cells have been shown to be more easily separated from solid tumors than are normal cells from corresponding tissues. Tumor cells have also been shown to be less adherent than normal cells to artificial substrates.

While the low adhesiveness of tumor cells contributes to the separation of cells from the primary tumor, metastasis is aided by the cells having some minimum degree of adhesion. The homotypic and heterotypic aggregation properties of tumor cells represent important biological features of malignancy because these properties of transformed cells contribute to the metastatic ability of neoplastic tumors. The concentration and size distribution of tumor cell clumps that enter the circulation play a significant role in the metastatic process. For example, intravenous injected tumor cells in clump form have a greater tendency to form metastases than do the same number of single tumor cells. Adhesion of cancer cells to other cells in the circulatory system is required for the cancer cells to escape from the circulation system. Cancer cells that remain in the circulation system are known to have a very short lifetime. Hence, blocking of the homotypic and heterotypic adhesion of cancer cells can prevent escape of metastatic cells from the blood into the tissues and may cause a dramatic reduction or even complete prevention of metastasis. 4 The process of cell-cell recognition, association and aggregation consists of multiple steps, and a number of models of such a multistep process have been proposed. Generally the initial step is specific recognition between two cells in which multivalent homo-and-heterotypic carbohydrate mediated interactions play a major role. Initial cell recognition through carbohydrate-carbohydrate or carbohydrate-protein (selectin) interaction is followed by protein-protein type adhesion, primarily mediated by Ca++-sensitive adhesion molecules such as cadherins, or by proteins of immunoglobulin superfamily, or by pericellular adhesive meshwork proteins consisting of fibronectin, laminin, and their receptor systems (integrin). The third step of cell adhesion is the establishment of intercellular junctions, e.g., "adherent junctions" and "gap junctions," in which a cell-cell communication channel is opened through specific structural proteins, and specialized cellular contacts such as tight junctions and desmosomes are formed.

Structural determinants participating in the homotypic and heterotypic aggregation of histogenetically different types of cells may be the carbohydrate determinants of the blood-group antigen (BGA) related glycoantigens. Recently, experimental evidence has been generalized that supports the concept that some of the BGA-related glycodeterminants which have been identified earlier as tumor associated carbohydrate antigens (TAC A) function as key adhesion molecules. The recent studies have shown that cell adhesion through carbohydrate-carbohydrate or carbohydrate-selectin interactions occur at an early initial state of the "cascade" multistep cell adhesion mechanism, and this reaction is a prerequisite for subsequent cell adhesion directed by integrin or immunoglobulin based adhesion. Usually cells co-express on their surface the multiple components involved in "cascade" cell adhesion mechanism, and thus, this multistep adhesion reaction could be triggered by initial carbohydrate-carbohydrate or carbohydrate-selectin interaction. Evidence has been presented that specific glycosphingolipid-glycosphingolipid interaction initiates cell-cell adhesion, and may cooperate synergistically with other cell adhesion systems such as those involving integrins. Thus, the key features of cancer cell adhesion are the preservation of cell recognition function and the initial reversible steps of cell-cell or cell-substrate 5 adhesion and the impairment of the ability to display secondary stable attachment, strong adhesion, and terminal tissue specific cell-cell and cell-substrate contacts. The profound defects in protein adhesive systems primarily mediated by the cadherin and integrin families of adhesion receptors is characteristic of malignant transformation and may contribute significantly to the abnormal locomotion, motility, invasion and metastasis of cancer cells. However, the acquisition of certain adhesive properties by malignant cells is extremely important for invasion, motility and metastasis. Typically, metastatic cancer cells lose the adhesive characteristics of their parent coherent tissues, but acquire adhesive properties similar to those of embryo and/or circulating normal cells (e.g. leukocytes and platelets).

Aberrant glycosylation of cell-membrane macromolecules is one of the universal phenotypic attributes of malignant tumors. A rather limited number of molecular probes based on monoclonal anticarbohydrate antibodies now enables the detection of over 90% of the most widespread human forms of cancer. One of the most important biological consequences of aberrant glycosylation is the expression of cell adhesion determinants on the surface of cancer cells. The most characteristic manifestation of aberrant glycosylation of cancer cells is neosynthesis (or ectopic synthesis), the synthesis of incompatible antigens and incomplete synthesis (with or without the accumulation of precursors) of the BGA-related glycoepitopes. BGA- related glycoepitopes are directly involved in the homotypic (tumor cells, embryonal cells) and heterotypic (tumor cells-normal cells) formation of cellular aggregates (e.g., Lewis X antigens; H-antigens, polylactosamine sequences; and T-and Tn-antigens), which was demonstrated in different experimental systems. BGA-related alterations in the tissue glycosylation pattern are detected in benign (premalignant) tumors with risk of malignant transformation, in primary malignant tumors, and in metastases.

Hence, they have been demonstrated as typical alterations in different stages of tumor progression. Therefore, the aberrant glycosylation in cancer is characterized by expression on the cell surface of tumor cells of certain BGA-related glycodeterminants. These changes were demonstrated as typical for different stages of tumor progression, including metastasis. The BGA-related glycodeterminants that are expressed on the surface of cancer cells function as cell adhesion molecules. They 6 are present in cancer blood serum in biologically active form and may either stimulate or inhibit cell-cell interactions. The important fact is that in serum of all normal individuals circulate the naturally occurring anticarbohydrate antibodies of the same specificity. The passage of metastatic cancer cells through blood and/or the lymph compartment of a host's body is one of the critical steps in metastatic dissemination of solid malignant neoplasms. Cancer cells that do not complete the transition quickly have exceedingly low survival rates in the circulatory system. There is a rapid phase of postintravasation (intramicro vascular) cancer cell death which is completed in less than 5 minutes and accounts for 85% of arrested cancer cells; this is followed by a slow phase of cell death, which accounts for the vast majority of the remainder. Mechanical trauma, which is a consequence of a shape transitions that occur when cancer cells enter and move along capillaries, has been considered as a most important factor contributing to the rapid death of the majority of cancer cells arrested in microvasculature of a different organs during metastatic dissemination.

Hence, inhibition of extravasation of cancer cells, blocking of their homotypic and heterotypic adhesion can prevent escape of metastatic cells from leaving the blood and entering the tissues. These considerations, as well as the analysis of cancer-related aberrations of cell adhesion mechanisms, suggest that agents that block cell adhesion may be of use in blocking metastasis. This therapy has been suggested as an additional complementary intervention for the current cancer treatment protocol, particularly designed to follow the surgical removal of a primary tumor.

The process of cell adhesion is also essential in the normal migration of cells. For example, in the healing of a wound, cells must migrate into the opening in the tissues in order to repair the opening. This cellular movement involves various classes of cells that move over the tissues surrounding the wound to reach the opening. Cellular adhesion is known to play a critical role in this type of cellular movement. Hence, compounds that enhance cellular adhesion are expected to enhance processes such as the healing of wounds. Similarly, the immune system both 7 when functioning properly and in autoimmune diseases involves specific cellular adhesive reactions.

While potentially therapeutic compounds that affect cell adhesion are known, these compounds tend to be large macromolecules such as antibodies or peptides having carbohydrate moieties attached thereto. Maintaining such large structures in the circulatory system and/or targeting them to specific tissues presents a number of well-known problems. In addition, the cost of manufacturing such compounds is quite high.

It is an object of the present invention to provide an improved class of compounds that inhibit the growth of cancer cells, induce apoptosis, and inhibit or enhance cell adhesion and methods for their use. It is a further object of the present invention to provide such compounds that consist of small molecular weight compounds. It is a still further object of the present invention provide such compounds that may be synthesized using conventional chemical techniques. It is yet another object of the present invention to provide such compounds and methods for their use that may be applied as antimetastatic agents. It is yet another object of the present invention to provide a method of enhancing the effect of existing cancer therapies. It is yet another object of the present invention to provide a method of combination cancer therapies. These and other objects of the present invention will become apparent to those skilled in the art from the following detailed description of the invention and the accompanying drawings.

8

SUMMARY OF THE INVENTION

The present invention comprises a class of molecules and methods for their use that alter cell adhesion, induce apoptosis, and inhibit cancer cell growth and metastasis. A method according to the present invention comprises bringing cells into contact with compounds that comprise an amine linked to a carbohydrate wherein the amine and the carbohydrate are linked to form a compound chosen from the group consisting of Schiff bases, N-glycosides, esters, and Amadori products. The carbohydrate is preferably a monosaccharide or a small oligosaccharide. The carbohydrate sub-unit may be chemical modified. The carbohydrate sub-unit is preferably a pentose such as arabinose, xylose, ribose, ribulose, a hexose such as fructose, deoxyfructose, galactose, glucose, mannose, tagatose, rhamnose, or a disaccharide based on two of the above such as maltose, lactose, maltulose, or lactulose. The amine subunit is preferably a primary or secondary amine. A method according to the present invention comprises bringing cells into contact with the compounds described above before, during or after administration of another cancer therapy. Another method according to the present invention comprises administering such compounds to a cancer patient by oral, intravenous, intranasal, subcutaneous, intramuscular or any other efficacious route of administration.

9 BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 illustrates the three types of compounds obtained from condensation reactions between glycine and glucose.

Figs. 2a, 2b, and 2c show the antimetastatic activity of synthetic glycoamines in experimental metastasis assay employing three murine cancer models: B16 melanoma; 3LL Lewis carcinoma, and MX-induced fibrosarcoma, respectively.

Fig. 3 illustrates the inhibition of colony formation in agarose by MDA-MB-435 human breast carcinoma cells by synthetic glycoamines.

Figs. 4a and 4b show the antimetastatic activity of synthetic glycoamines in the MDA-MB-435 model of human breast cancer metastasis in nude mice.

Fig. 5 shows the inhibition of homotypic aggregation of MDA-MB- 435 cells by synthetic glycoamines.

Figs. 6a and 6b illustrate the induction of apoptosis in target cells by synthetic glycoamines as determined by the TUNEL assay (a) and DNA fragmentation analysis (b).

Fig. 7 shows inhibition of clonogenic growth of human prostate carcinoma cells by antimetastatic synthetic glycoamines.

Figs. 8a and 8b illustrate the results of combination therapy experiments employing highly metastatic human breast carcinoma cell line MDA- MB-435.

Fig. 9 shows the results of combination therapy experiments employing human colon carcinoma cell line Colo205.

Figs. 10a, 10b and 10c illustrate the results of combination therapy experiments employing highly metastatic human breast carcinoma cell line MDA- MB-435 and a variable schedule of drug application.

Fig. 11 shows a dose-response analysis of the inhibition of clonogenic growth of DU145 human prostate carcinoma cells by Taxol with and without addition of SSGA-19. 10 Fig. 12 shows a dose-response analysis of the inhibition of clonogenic growth of DU145 human prostate carcinoma cells by synthetic glycoamine analog SSGA-19.

Fig. 13 shows the results of a clonogenic growth assay of SSGA-70, Taxol and a combination therapy using SSGA-70 and Taxol.

Fig. 14 shows the results of a clonogenic growth assay of SSGA-70, cis-platin and a combination therapy using SSGA-70 and cis-platin.

Fig. 15 shows the results of a clonogenic growth assay of SSGA-72, Taxol and a combination therapy using SSGA-72 and Taxol. Fig. 16 shows a dose-response analysis of the inhibition of clonogenic growth of highly metastatic human breast carcinoma cell line MDA-MB-435 by Taxol with and without the addition of SSGA-70.

Fig. 17 shows a dose-response analysis of the inhibition of clonogenic growth of highly metastatic human breast carcinoma cell line MDA-MB-435 by cis- platin with and without the addition of SSGA-70.

Fig. 18 shows a dose-response analysis of the inhibition of clonogenic growth of highly metastatic human breast carcinoma cell line MDA-MB-435 by Taxol with and without the addition of SSGA-72.

Fig. 19 shows dose response curves in clonogenic growth assays for fructose alone and three fructose-containing synthetic glycoamines.

Fig. 20 shows dose response curves in clonogenic growth assays for lactose alone and three lactose-containing synthetic glycoamines.

Fig. 21 illustrates the induction of apoptosis in target cells by SSGA- 70, Taxol and SSGA-70 plus Taxol as determined by the TUNEL assay. Fig. 22 illustrates the induction of apoptosis in target cells by SSGA-

19, Taxol and SSGA-19 plus Taxol as determined by the TUNEL assay.

Definitions Standard cancer therapy means any method of anticancer treatment employed in current medical practice such as surgery, chemotherapy, γ- or X- irradiation directed at inhibition of growth, destruction or elimination of cancer cells. Amine means any amino group bearing compound. 11 DETAILED DESCRIPTION OF THE INVENTION

The present invention comprises a class of compounds that either enhance or inhibit cellular adhesion, depending on the particular compound chosen and the target cell type. In addition, the compounds inhibit cancer cell metastasis and induce apoptosis in target cells. The simplest molecules in the class may be viewed as having two sub-units. The first sub-unit is an amine, and the second sub-unit is a carbohydrate. The amine may be joined to the carbohydrate by any condensation of the carbohydrate and the amine. For example, esters, Schiff bases, N-glycosides, and Amadori compounds may be used. Here, the aldehyde group and/or one or more of the hydroxyl groups of the carbohydrate are substituted by the corresponding covalent bonding with the amine. As will become clear from the following discussion, compounds according to the present invention may be synthesized and purified via conventional organic chemical procedures; hence, the compounds of the present invention may be obtained at far less cost than other potential affectors of cell adhesion, cancer cell growth and metastasis inhibitors, or apoptosis inducers that require complex chemistry and/or fermentation to provide the chemicals or their precursors.

Refer now to Fig. 1 which illustrates the chemical reactions for the compounds according to the present invention that utilize the amino acid glycine and the sugar glucose. The condensation of a carboxyl group of an amino acid, namely glycine, with a hydroxyl group of carbohydrate, namely glucose, leads to the formation of an ester bond affording glycosyl amino acidate which is shown at 11. The amino acid-aldose condensation with the involvement of the amino and aldehyde groups occurs much more readily and may lead to the formation of Schiff bases (open chain of carbohydrate), or N-glycosides(12) (cyclic form of carbohydrate) with subsequent development of Amadori compounds(13). It will be apparent to those skilled in the art that the glycine can be replaced by any amine in the scheme shown in Fig. 1, and the glucose can be replaced by any sugar. Preparation of Amadori Compounds The most stable class of condensation product of an amino acid and a carbohydrate is an Amadori compound. The Amadori compounds are the preferred 12 compounds because of their high biological activity, stability, relative simplicity of synthesis, isolation and purification in large quantities. The synthesis of Amadori compounds may be carried out as follows: A suspension of 0.2 mol of sugar (e.g., anhydrous D-glucose, D-galactose or D-lactose monohydrate, etc.), 2.0 sodium bisulfite in 60 mL of methanol and 30 mL of glycerol is refluxed for 30 min., followed by the addition of 0.05-0.09 mol of amino acid and 8 mL of acetic acid. The solution is refluxed until about 80% of the amino acid is reacted, as evidenced by TLC. The resulting brown, syrupy solution is diluted with 1 volume of water, placed on a 2 cm by 30 cm column of Amberlite IRN-77 ion exchange resin (hydrogen form) pretreated with 8 mL of pyridine. The column is eluted with water, followed by 0.2 N ammonium hydroxide or, if necessary, by a buffer that was 0.2 M in pyridine and 0.4 in acetic acid. Fractions of approximately 25 mL are collected. Early fractions contain D-glucose, uncharged pigments and D-glucose-derived degradation products. The Amadori compound usually elute next and are collected until the concentration becomes too low. The combined fractions, which contain Amadori compound, are evaporated to 100 mL in vacuo, decolorized with charcoal (2.0 g) and evaporated in vacuo at 30° to syrups.

Some of the Amadori compound, along with unreacted amino acid elute near the end of the water wash and at the beginning of the ammonium hydroxide wash. The combined fractions, which contain Amadori compound, are evaporated to 100 mL in vacuo and decolorized with charcoal (2.0 g). This solution is placed on a second 2 cm by 30 cm column of Amberlite IRN-77 (pyridinium form, pretreated with 10 mL of acetic acid). The column is eluted with water and 25 mL fractions collected. The Amadori compounds usually elute immediately. Fractions containing the desired products are evaporated in vacuo at 30°C to syrups.

In the preferred embodiment of the present invention, the reaction conditions as well as separation and purification methodology of Amadori products may be optimized as follows: Methanol-glycerol mixture(s) as solvent provides the optimal reaction temperature (80°C) at refluxing, necessary solubility for carbohydrates and amino acids, and dehydration conditions to shift the equilibrium toward the N-glycosides. Small amounts of acetic acid and sodium pyrosulfite are 13 necessary to create optimal acidity of the reaction mixtures (pH ca. 5.0) to catalyze the Amadori rearrangement which competes with acid hydrolysis to the starting reagents and to optimize the reducing conditions (eliminating SO₂) to prevent oxidative browning of Amadori products. These conditions lead to over 90% conversion of starting amino acids if a 3-4 fold molar excess of carbohydrate is employed. The progress of the reaction may be readily monitored by TLC analysis using ninhydrin as the spray reagent.

The method of isolation of Amadori product from reaction mixture containing Amadori product, amino acid, sugars, and browning products is based on application of ion-exchange chromatography. The reaction mixture is diluted by water and then loaded on a cationite column in H+- or pyH+- form (for acid labile Amadori products). Amino acids, Amadori product and charged browning products are retained on ion-exchange resin, and noncharged compounds solvent, sugar and majority of browning products) are eluted by water. The next elutents usually are the aqueous pyridine, acetic acid, ammonia and their mixture depending on individual properties of corresponding Amadori product and amino acid. The pH range is chosen to provide separation of Amadori product and amino acid on the column due to difference in their acid-base properties. The portion of eluate containing pure Amadori product is evaporated and residue crystallized from convenient solvent or mixture. In practice, pure final Amadori product (95% or more) with yield range of 10-40% from corresponding amino acid is obtained. The chromatographic and structural characterization of synthetic products may be performed using TCL, reversed, ion-exchange and normal-phase HPL, FAB-MS, elemental analysis, NMR, amino acid and carbohydrate analysis and pH-potentiometric analysis, optical rotation, X-ray analysis.

Preparation of Schiff Base Compounds

The sodium salts of the Schiff bases, compounds SSGA-22 through 30 (See Table I below), may be prepared by the following procedure. The appropriate amino acid (10 mmol) is added to a solution of 0.23 g (10 mmol) of metallic sodium in 80 mL of anhydrous methanol, and the suspension is then refluxed until all solid is dissolved. To the resulting solution, 10 mmol of carbohydrate is added and this 14 mixture is stirred at 25 to 40°C under inert atmosphere until the solution is clear. Dry diethyl ether (usually 200 - 400 mL) is then poured carefully into the reaction mixture under vigorous stirring to precipitate desired product as amorphous or microcrystalline mass. The product is separated with filtration, washed with ether and dried over CaCl₂, in vacuo.

Preparation of Ester Compounds

The synthesis of compounds SSGA-20, 21, 37, and 38 (See Table I below) as their hydrochlorides utilizes the following procedure: A solution of 5 mmol of Boc-amino acid, imidazole (1.02 g, 15 mmol) and anhydrous sugar (1.80 g, 10 mmol) in 60 mL of dry pyridine is prepared and cooled to 0°C.

Dicyclohexylcarbodiimide (DCC, 1.03 g, 5 mmol) is then added and the reaction mixture is stirred in an ice bath for 4 hours and at room temperature for an additional 12 hours. A precipitate of dicyclohexylurea is filtered off and the filtrate is evaporated in vacuo. The residue is partitioned between ethyl acetate (40 mL) and cold 10% citric acid in water (40 mL). The organic layer is washed with water, dried over Na₂SO₄ and evaporated in vacuo. The residue is crystallized from chloroform or methanol-chloroform, yielding the protected ester with 40-70% yield. This is dissolved in 15 mL of 1 N solution of HCI in methanol or acetic acid and stirred at room temperature for an hour followed by addition of dry diethyl ether. The precipitate is collected by filtration and recrystallized from diethyl ether-THF.

The procedure for the synthesis of compounds SSGA-52 through 55 as their hydrochlorides utilizes the following procedure: To a solution of 5 mmol of Boc-amino acid and methyl α-D-glucopyranoside (1.94 g, 10 mmol) in 60 mL of dry acetonitrile a DCC (1.03 g, 5 mmol) is added at - 10°C. The reaction mixture is stirred at 0°C for 5 h and then overnight at room temperature. The protected ester is then isolated as described above with reference to SSGA-20, etc. Modifications of the Basic Structure

In addition to the simple compounds consisting of an amino acid linked to a sugar, active compounds which are modifications of the basic structure have also been identified. These modifications may be separated into four classes. The first class involves the substitution of a small polypeptide for the amino acid. 15 The second group involves substituting a polysaccharide for the sugar. The third class involves optical isomerization of an amino acid or modifications to the amino group, carboxyl group, hydrocarbon chains, or side chain group of the amino acids by covalently bonding other groups to one or more of these groups. Compounds SSGA- 8, SSGA-10, SSGA-13, SSGA-39, SSGA-45, SSGA-56, SSGA-63, SSGA- 66, and SSGA-68 belong to this class. Two carbohydrate residues may be linked to a single amino group (SSGA-51, 61, 62 or 63), or a compound containing several amino groups may have a sugar linked to each amino group (SSGA-44). Finally, one or more hydroxyl groups of the carbohydrate may be modified. For example, the hydroxyl group of the compounds based on D-glucose may be methylated to form compounds such as methyl α-D glucopyranoside. Compounds SSGA-52 through SSGA-54 belong to this fourth class. For the purposes of the following discussion, the simplest class of molecules consisting of an amino acid coupled to a sugar will be referred to as the basic class. Glycoamines Comprising Amines Other than Amino Acids

The glycoamines discussed above are formed by condensation reactions between amino acids and reducing sugars. However, amino acids are not the only class of molecules that may undergo the condensation reaction with reducing sugars. Primary and secondary amines react with reducing sugars to form N- glycosides, Schiff bases, or Amadori compounds. Glycoamines comprising structurally diverse families of primary and secondary amines have been shown to exhibit the same useful characteristics of glycoamines comprising amino acids. Glycoamines comprising amines in each of the following classes were synthesized and tested: i) primary amines (butylamine; 1,6-diaminohexane; p-toluidine); ii) secondary amines (N-methylaniline; piperidine; morpholine); iii) linear amines (butylamine; 1,6-diaminohexane); iv) cyclic amines (N-methylaniline; piperidine; p-toluidine; morpholine); v) aromatic amines (N-methylaniline; p-toluidine); vi) aliphatic amines (morpholine; piperidine; 1,6-diaminohexane; butylamine); 16 vii) monoamines (N-methylamine; piperidine; p-toluidine; morpholine; butylamine); viii) polyamines (1,6-diaminohexane). Compounds with different mono- and disaccharides, such as fructose, tagatose, and lactose, also may be used in the invention. Representative compounds are listed as SSGA-70 through SSGA-79 in Tables 1 and 2. Dosage and Method of Administration

Various methods of determining the appropriate dose for use in methods according to the present invention are known in the art. The following steps is one approach that may be used to implement the method of cancer therapy of the present invention into clinical practice:

1) Determine the effective therapeutic concentration and pharmacokinetic effects in blood or other body fluids such as lymph, of mice of the therapeutic compound by measuring the blood level of the compound at different time points during administration;

2) Establish the therapeutic protocol for humans based on determination of the time and dose, regimen of administration, and route of administration (oral, intravenous, intranasal, subcutaneous, intramuscular, etc.) that is necessary to achieve the effective therapeutic concentration and pharmacokinetics of the compound in the body fluids of human subjects; and

3) Apply the established therapeutic protocol for humans in clinical practice.

Different therapeutic applications may require certain modifications of the therapeutic protocol. For example, implementation of the metastasis chemoprevention protocol may require administration of the compound for a long period of time. Oral administration of the drug may be preferable for this therapeutic protocol. Using the method of the present invention in combination cancer therapy may require administration of the compound for a relatively limited time coinciding with standard cancer therapies. However, a higher dose of the compound and more precise control of the pharmacokinetic effects may be required. In this situation, intravenous administration may be preferable. 17

Exemplary Compounds

Eighty-one exemplary compounds have been synthesized and all of these can be shown to affect cell adhesion in one or more cell adhesion assays. A summary of the chemical compounds investigated to date is given in Table I, below. The corresponding amine, method of linkage, and carbohydrate for a compound may be deduced from the compound's name. The full chemical name of each of the compounds listed in Table I may be found in Table II, below. Compounds SSGA-1 through SSGA-19, SSGA-31 through SSGA-36, and SSGA-39 through 51 are Amadori compounds. Compounds SSGA-22 through 30 are Schiff bases. Compounds SSGA-20, SSGA-21, SSGA-37, SSGA-38, and SSGA-52 through SSGA-55 are glycosyl esters of amino acids.

Some of the members of this group promote cell adhesion and some inhibit cell adhesion. In addition, some members promote cell adhesion in one cell type and inhibit cell adhesion in other cell types. The specific effect produced depends on the type of amino acid, sugar, coupling bond and the target cell type. Members of this group have been shown to inhibit cancer metastasis, inhibit cell growth, and induce apoptosis in target cells.

18 Table I Names of Synthetic Glycoamine Structural Analog

SSGA- 1 N-( 1 -Deoxy-D-fructos- 1 -yl)-β-alanine

SSGA-2 N-(l-Deoxy-D fructos-l-yl)-glycine

SSGA-3 N-(l-Deoxy-D fructos- l-yl)-L-phenylalanine

SSGA-4 N-(l-Deoxy-D fructos-l-yl)-L-tyrosine

SSGA-5 N-(l -Deoxy-D fructos-l-yl)-L-isoleucine

SSGA-6 N-(l-Deoxy-D fructos- l-yl)-L-aspartic acid

SSGA-7 N-(l-Deoxy-D fructos-l-yl)-L-glutamic acid

SSGA-8 N-ε-(l -Deoxy-D fructos-l-yl)-N-α-formyl-L-lysine

SSGA-9 N-(l -Deoxy-D fructos-l-yl)-γ-aminobutyric acid

SSGA- 10 N-( 1 -Deoxy-D fructos- 1 -yl)-ε-aminocaproic acid

SSGA-11 N-(l-Deoxy-D fructos- l-yl)-L-tryptophan

SSGA-12 N-(l-Deoxy-D fructos- l-yl)-L-leucine

SSGA- 13 N-(l -Deoxy-D fructos- l-yl)-D-leucine

SSGA-14 N-(l-Deoxy-D fructos- lyl)-L-alanine

SSGA-15 N-(l-Deoxy-D fructos- lyl)-L-valine

SSGA-16 N-(l-Deoxy-D fructos- lyl)-L-proline

SSGA- 17 N-( 1 -Deoxy-D-tagatos- 1 -yl)-L leucine

SSGA-18 N-(l -Deoxy-D-maltulos-1 -yl)-L-leucine

SSGA- 19 N-(l -Deoxy-D-lactulos- 1 -yl)-L-leucine

SSGA-20 6-0-(L-Prolyl)-D-glucose

SSGA-21 6-0-(L-Phenylalanyl)-D-glucose

SSGA-22 N-l(l-Deoxy-D-glucos-l-yl)-L-proline Na-salt

SSGA-23 N- 1 ( 1 -Deoxy-D-glucos- 1 -yl)-L-phenylalanine Na-salt

SSGA-24 N- 1 ( 1 -Deoxy-L-rhamnos- 1 -yl)-L-alanine Na-salt 19

SSGA-25 N- 1 ( 1 -Deoxy-D-galactos- 1 -yl)-L-alanine Na-salt

SSGA-26 N-l(l-Deoxy-D-glucos-l-yl)-L-alanine Na-salt

SSGA-27 N- 1 ( 1 -Deoxy-D-mannos- 1 -yl)-L-alanine Na-salt

SSGA-28 N-l(l-Deoxy-L-arabinos-l-yl)-L-alanine Na-salt

SSGA-29 N-l(l-Deoxy-D-maltos-l-yl)-L-alanine Na-salt

SSGA-30 N-l(l-Deoxy-D-xylox-l-yl)-L-alanine Na-salt

S SGA-31 N- 1 ( 1 -Deoxy-D-ribulos- 1 -yl)-L-phenylalanine

SSGA-32 N- 1 ( 1 -Deoxy-D-fructos- 1 -yl)-L-threonine

SSGA-33 N-(l -Deoxy-D-maltulos- 1 -yl)-L-phenylalanine

S SGA-34 N-( 1 , 6-Dideoxy-L-fructos- 1 -yl)-L-proline

SSGA-35 N-(l -Deoxy-D-tagatos- 1 -yl)-L-phenylalanine

SSGA-36 N-(l -Deoxy-D-lactulos- 1 -yl)-L-phenylalanine

SSGA-37 6-0-(L-Valyl)-D-mannose

SSGA-38 6-0-(L-Prolyl)-D-galactose

SSGA-39 N-(l -Deoxy-D-fructos- l-yl)-δ-amino valeric acid

SSGA-40 N-(l -Deoxy-D-fructos- l-yl)-L-serine

S SGA-41 N-( 1 -Deoxy-D-lactulos- 1 -yl)-L-proline

S SGA-42 N-( 1 -Deoxy-D-lactulos- 1 -yl)-L-valine

SSGA-43 N-(l -Deoxy-D-fructos- 1 -yl)-L-methionine

SSGA-44 N,N'-Di (l-deoxy-D-fructos-l-yl)-L-lysine

SSGA-45 N-α-( 1 -Deoxy-D-fructos- 1 -yl)-N-ε-formyl-L- lysine

SSGA-46 N-α-(l -Deoxy-D-fructos- l-yl)-L-asparagine

SSGA-47 N-( 1 -Deoxy-D-fructos- 1 -yl)-L-hydroxyproline

SSGA-48 N-(l -Deoxy-D-tagatos- l-yl)-L-proline

S SGA-49 N-( 1 -Deoxy-D-tagatos- 1 -yl)-L-valine 20

SSGA-50 ^-(1 -Deoxy-D-fructos- 1 -yl)-L-histidine

SSGA-51 N,N-Di (l-deoxy-D-fructos-l-yl)-glycine

SSGA-52 Methyl 6-O-(glycyl)-α-D-glucopyranoside

SSGA-53 Methyl 2,3,4-tri-O-(glycyl)-6-O-(L-alanyl)-α-D-glucopyranoside

SSGA-54 Methyl 6-O-(L-alanyl)-α-D-glucopyranoside

SSGA-55 Methyl 2,3,-di-O-(L-alanyl)-α-D-glucopyranoside

SSGA 56 N-(l -Deoxy-D-lactulos- l-yl)-D-leucine

SSGA 57 N-(l -Deoxy-D-lactulos- l-yl)-L-isoleucine

SSGA 58 N-( 1 -Deoxy-D-lactulos- 1 -yl)-glycine

SSGA 59 N-(l -Deoxy-D-fructos- l-yl)-L-arginine

SSGA 60 N-(l-Deoxy-D-lactitol-l-yl)-L-leucine

SSGA 61 N,N-Di(l-deoxy-D-fructos-l-yl)-γ-aminobutyric acid

SSGA 62 N, N-Di (1-deoxy-D-fructos-l-yl) β-alanine

SSGA 63 N-ε, N-ε-Di (1- deoxy-D-fructos-l-yl)-N-α-formyl-L-lysine

SSGA 64 N-(2-Deoxy-D-galactos-2-yl)-glycine

SSGA 65 N-(2-Deoxy-D-glucos-2-yl)- glycine

SSGA 66 N-(l-Deoxy-D-fructos-l-yl)-L-phenylglycine

SSGA 67 N-(l -Deoxy-D-fructos- l-yl)-sarcosine

SSGA 68 N-(l -Deoxy-D-fructos- l-yl)-D-tyrosine

SSGA 69 N-(l -Deoxy-D-tagatos- l-yl)-glycine

SSGA 70 N,N^;-Di( 1 -deoxy-D-lactulos- 1 -yl)- 1 ,6-diaminohexane

SSGA 71 N-( 1 -Deoxy-D-lactulos- 1 -yl)-N-methylaniline

SSGA 72 Ν-( 1 -Deoxy-D-fructos- 1 -yl)-N-methylaniline

SSGA 73 N-( 1 -Deoxy-D-tagatos- 1 -yl)-N-methylaniline

SSGA 74 Ν-( 1 -Deoxy-D-fructos- 1 -yl)-piperidine 21

SSGA 75 N-( 1 -Deoxy-D-fructos- 1 -yl)-p-toluidine

SSGA 76 N-( 1 -Deoxy-D-fructos- 1 -yl)-morpholine

SSGA 77 N-(l-Deoxy-D-fructos-I-yl)-butylamine

S S G A 78 1 -Deoxy-D-fructos- 1 -ylamine

SSGA 79 N-(l -Deoxy-D-fructos- l-yl)-glucosamine

SSGA 80 N-( 1 -Deoxy-D-fructos- 1 -yl)-cycloleucine

SSGA 81 N^α-( 1 -Deoxy-D-fructos- 1 -yl)-N^α-acetyl-L-lysine

22 Table II Full systematic names of synthetic glycoamine structural analogs.

SSGA-1 N-(l-Deoxy-D-arab o-hexulos-l-yl)-3-aminopropanoic acid

SSGA-2 N-(l-Deoxy-D-αrab/«o-hexulos-l-yl)-aminoethanoic acid

SSGA-3 N-(l-Deoxy-D-αrαό o-hexulos-l-yl)-(S)-2-amino-3-phenylpropanoic acid

SSGA-4 N-( 1 -Deoxy-D- rαbwo-hexulos- 1 -yl)-(S)-2-amino-3-(4- hydroxyphenyl)-propanoic acid

SSGA-5 N-(l-Deoxy-D-αrab/«o-hexulos-l-yl)-(2S,3S)-2-amino-3- methylpentanoic acid

SSGA-6 N-(l-Deoxy-D-αraό o-hexulos-l-yl)-(S)-2-aminobutane-l,4-dioic acid

SSGA-7 N-(l-Deoxy-D-αraόz^'no-hexulos-l-yl)-(S)-2-aminopentane-l,5-dioic acid

SSGA-8 (S)-6-(l-Deoxy-D-αrab o-hexulos-l-amino)-2-N- formylaminohexanoic acid

SSGA-9 N-(l-Deoxy-D-βra5wo-hexulos-l-yl)-4-aminobutanoic acid

SSGA-10 N-(l-Deoxy-D-αrα6z«ø-hexulos-l-yl)-6-aminohexanoic acid

SSGA-11 (S)-2-(l-Deoxy-D-αrαδ o-hexulos-l-amino)-3-(indol-3-yl)-propanoic acid

S SGA- 12 N-( 1 -Deoxy-D-αrab -hexulos- 1 -yl)-(S)-2-amino-4-methylpentanoic acid

S SGA- 13 N-( 1 -Deoxy-D- rαb o-hexulos- 1 -yl)-(R)-2-amino-4-methylpentanoic acid

SSGA-14 N-(l-Deoxy-D-αrabwo-hexulos-l-yl)-CSj-2-aminopropanoic acid

SSGA-15 N-(l-Deoxy-D-αrαf o-hexulos-l-yl)- S -2-amino-3-methylbutanoic acid

SSGA-16 fS)-l-(l-Deoxy-D-αrαbz^'«o-hexulos-l-yl)- 2-pyrrolidine carboxylic acid

SSGA- 17 N-(l -Deoxy-D-Zyxo-hexulos- 1 -yl)-(S -2-amino-4-methylpentanoic acid

SSGA- 18 N-(l -Deoxy-4-O-(α-D-glucopyranos- 1 -yl)-D-αra6 o-hexulos- 1 -yl)- CSJ-2-amino-4-methylpentanoic acid 23

SSGA-19 N-(l-Deoxy-4-O-(β-D-galactopyranos-l-yl)-D-αra& o-hexulos-l-yl)- (SJ-2-amino-4-methylpentanoic acid

SSGA-20 6-O-(CSj-2-pyrrolidine carboxyl)-D-glucose

SSGA-21 6-O-((S -2-amino-3-phenylpropanoyl)-D-glucose

SSGA-22 fSH-(l -Deoxy-D-glucos- l-yl)-2-pyrrolidine carboxylic acid

SSGA-23 N-( 1 -Deoxy-D-glucos- 1 -yl)-fS -2-amino-3-phenylpropanoic acid

SSGA-24 N-(l,6-Dideoxy-L-mannos-l-yl)-(S)-2-aminopropanoic acid

SSGA-25 N-(l -Deoxy-D-galactos- l-yl)-(S)-2-aminopropanoic acid

SSGA-26 N-(l -Deoxy-D-glucos- l-yl)-(S)-2-aminopropanoic acid

SSGA-27 N-(l-Deoxy-D-mannos-l-yl)-(S)-2-aminopropanoic acid

SSGA-28 N-(l-Deoxy-L-αrøbz^'nos-l-yl)-(S)-2-aminopropanoic acid

SSGA-29 N-(l-Deoxy-4-O-(α-D-glucopyranos-l-yl)-D-glucos-l-yl)-(S)-2- aminopropanoic acid

SSGA-30 N-(l-Deoxy-D-xylos-l-yl)-(S)-2-aminopropanoic acid

SSGA-31 N-( 1 -Deoxy-D-eryt zro-pentulos- 1 -yl)-(S)-2-amino-3-phenylpropanoic acid

SSGA-32 N-(l-Deoxy-D-αrab o-hexulos-l-yl)-(2S,3i?)-2-amino-3- hydroxybutanoic acid

SSGA-33 N-( 1 -Deoxy-4-0-(α-D-glucopyranos- 1 -yl)-D-αrøbz«o-hexulos- 1 -yl)- (S)-2-amino-3-phenylpropanoic acid

SSGA-34 (S)- 1 -( 1 ,6-Deoxy-L-αrαbznø-hexulos- 1 -yl)-2-pyrrolidine carboxylic acid

SSGA-35 N-(l-Deoxy-D-/yxo-hexulos-l-yl)-(S)-2-amino-3-phenylpropanoic acid

SSGA-36 N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-αraσmo-hexulos- 1 -yl)- CS)-2-amino-3-phenylpropanoic acid

SSGA-37 6-O-( S 2-amino-3-methylbutanoyl)-D-mannose

SSGA-38 6-0-((S)-2-pyrrolidine carboxyl)-D-galactose

SSGA-39 N-(l -Deoxy-D-αraό/«o-hexulos-l-yl)-5-aminopentanoic acid 24

SSGA-40 N-(l-Deoxy-D-αrα/ z^'«o-hexulos-l-yl)-(S)-2-amino-3-hydroxypropanoic acid

SSGA-41 (S)- 1 -( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-αrabz^'«o-hexulos-l- yl)-2-pyrrolidine carboxylic acid

SSGA-42 N-(l-Deoxy-4-O-(β-D-galactopyranos-l-yl)-D-βrα/3t«o-hexulos-l-yl)- (S -2-amino-3-methylbutanoic acid

SSGA-43 N-(l-Deoxy-D-αrøbz^'«o-hexulos-l-yl)-(S)-2-amino-4- methylthiobutanoic acid

SSGA-44 N,N'-Di(l-deoxy-D-αrα/ o-hexulos-l-yl)-(S)-2,6-diaminohexanoic acid

SSGA-45 S -2-(l-Deoxy-D-flra3z>zo-hexulos-l-amino)-6-N- formylaminohexanoic acid

SSGA-46 (S)-3-(l-Deoxy-D-αrflbmo-hexulos-l-amino)-3-carboxypropanamide

SSGA-47 (2S,4i?)-l-(l-Deoxy-D-αrαbz^'no-hexulos-l-yl)-4-hydroxy-2-pyrrolidine carboxylic acid

SSGA-48 fS)-l-(l-Deoxy-D-/y^ -hexulos-l-yl)-2-pyrrolidine carboxylic acid

SSGA-49 N-(l-Deoxy-D-/y σ-hexulos-l-yl)-(S)-2-amino-3-methylbutanoic acid

SSGA-50 CS -2-(l-Deoxy-D-arabz>zo-hexulos-l-amino)-3-(lH-imidazol-4-yl)- propanoic acid

SSGA-51 N,N-Di(l-deoxy-D-αrαb o-hexulos-l-yl)-aminoethanoic acid

SSGA-52 Methyl 6-0-(2-aminoethanoyl)-α-D-glucopyranoside

SSGA-53 Methyl 2,3,4-tri-O-(2-aminoethanoyl)-6-O-((S)-2-aminopropanoyl)-α- D-glucopyranoside

SSGA-54 Methyl 6-0-(CS)-2-aminopropanoyl)-α-D-glucopyranoside

SSGA-55 Methyl 2,3-di-0-((S)-2-aminopropanoyl)-α-D-glucopyranoside

SSGA-56 N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )- (R)-2-amino-4-methylpentanoic acid

SSGA-57 N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )- (2S, 3S)-2-amino-3-methylpentanoic acid

SSGA 58 N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )- aminoethanoic acid 25

SSGA-59 N-(l-Deoxy-D-arabino-hexulos-l-yl)-(S)-2amino-5-guanidinovaleric acid

SSGA 60 N-(D-gluco-2, 3, 5, 6-Tetrahydroxy-4-O-(β-D-galactopyranos-l-yl)- hexyl)-(S)-2-amino-4-methylpentanoic acid

SSGA-61 N, N-Di(2-deoxy-D-arabino-hexulos- 1 -y 1 )-4-aminobutyric acid

SSGA-62 N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid

S SGA-63 (S)-6-(Di( 1 -deoxy-D-arabino-hexulos- 1 -y 1 )-amino)-2-N- formylaminohexanoic acid

S SGA-64 2-Deoxy-2-carboxymethylamino-D-galactopyranose

SSGA-65 2-Deoxy-2-carboxymethylamino-D-glucopyranose

SSGA-66 N-(l -Deoxy-D-arabino-hexulos- l-yl)-(S)-2-amino-2-phenylethanoic acid

SSGA-67 N-(l-Deoxy-D-arabino-hexulos-l-yl)-N-methylaminoethanoic acid

SSGA-68 N-( 1 -Deoxy-D-arabino-hexulos- 1 -y 1 )-(R)-2-amino-3-(4- hydroxyphenyl)-propanoic acid

SSGA-69 N-(l-Deoxy-D-lyxo-hexulos-l-yl)-aminoethanoic acid

SSGA-70 N,N ^'-Di(l -deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 - yl)- 1 ,6-diaminohexane

S SGA-71 N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- N-methylaniline

SSGA-72 N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N-methylaniline

SSGA-73 N-( 1 -Deoxy-D-lyxo-hexulos- 1 -yl)-N-methylaniline

SSGA-74 N-(l -Deoxy-D-arabino-hexulos- l-yl)-piperidine

SSGA-75 N-(l -Deoxy-D-arabino-hexulos- l-yl)-4-methylaniline

SSGA-76 N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-morpholine

SSGA-77 N-(l -Deoxy-D-arabino-hexulos- l-yl)-butylamine

SSGA-78 1 -Deoxy-D-arabino-hexulos- 1-ylamine

S SGA-79 N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-2-amino-2-deoxy-D-glucose 26

S SGA-80 N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- 1 -ammocyclopentanecarboxylic acid

SSGA-81 (S)-6-(l -Deoxy-D-arabino-hexulos- l-amino)-2-N-acetylaminohexanoic acid

27 Biological Activity

The compounds listed in Table I have been tested in one or more of a panel of 9 assays for their ability to promote or inhibit cell adhesion. The test results are summarized in Table III. The panel of tests can be divided into three classes of tests. In the first class of tests (Tests 1-4 in Table III), the ability of a compound according to the present invention to inhibit or promote cell adhesion as measured by an in vitro murine cancer assay was determined, this test will be referred to as the cell aggregation assay in the following discussion. Tumor cells were obtained from the indicated tumor tissue by standard trypsinization procedures. Then, 10 cells were cultured at 37°C in 5% CO₂ by using RPM1 1640 containing 10% fetal calf serum, 2 mM glutamine, and 1 mM pyruvate, 100 IU of penicillin per mL, 20 μg of gentamicin per mL, and 100 IU of streptomycin per mL (growth medium). The cells were cultured with and without an adhesion affector according to the present invention. The concentration range for the tested compounds was 20μM to 15 mM. The cells were incubated for periods of 24-72 hours and 5 days in 0.4-1.0 mL (final volume) of growth medium in wells of a 96-well cell culture plate. The aggregates containing more than 4-5 cells (in suspension and substrate-attached) in each well were counted. Live cell counts were obtained by xrypan blue dye exclusion.

The second class of assay (Fig. 2 and Tests 5-7 in Table III) involves the measurement of metastatic activity in vivo. The assay was carried out as follows: Cancer cells of the indicated type were incubated for 1 hour in 5% CO₂ at 37°C in RPMI-1640 medium with and without addition of 1 mM (final concentration) of the tested compounds. Subsequently 2x10 melanoma or carcinoma cells were injected into the tail vein of C57B1 2-3 month old male mice and 21 days later, the lung metastases were counted. Similarly, 0.25x10 fibrosarcoma cells were injected into the tail vein of BALB/c 8-10 week old male mice and 21 days later, the lung metastases counted. All three general inhibitors of in vitro cancer cell aggregation showed a significant inhibition of in vivo experimental lung metastasis after intravenous inoculation of B16 melanoma cells. SSGA-12 and SSGA-13 have caused a 70% and 71% inhibition of lung colonization, respectively. Inhibition of B 16 28 melanoma lung metastasis also showed that synthetic compound SSGA-19 was inhibitory with a 63% of inhibition of lung colonization. The 2 most effective synthetic inhibitors of in vitro melanoma cell aggregation also inhibited lung metastasis the most. SSGA-9 and SSGA-10 inhibited the lung colonization by melanoma cells at 79% and 87%, respectively. For comparison, SSGA-5 which is not an inhibitor of the B16 melanoma cell line in the in vitro aggregation test is only a weak inhibitor in vivo. SSGA-5 inhibited lung colonization only 35% in the above described assay.

The third class of assays (Tests 8-9 in Table III) will be referred to as the in vitro human cancer assay. The MDA-MB-435 human breast carcinoma cell line was isolated originally from pleural effusion of a patient with breast carcinoma and was found to be highly metastatic from the mammary fat pad (m.f.p.) tumors as well as after i.v. injection in nude mice.

The TXM-13 human melanoma cell line were originally isolated from brain metastases and were established from surgical specimens from melanoma patients at The University of Texas M.D. Anderson Cancer Center (Houston, TX). TXM-13 human melanoma cell line was found to be highly tumorigenic and metastatic in nude mice.

The metastatic and tumorigenic properties of human melanoma and breast carcinoma cell lines in nude mice were found to correspond well with their colony-forming efficiency in dense agarose. Hence, the tests were carried out on agarose.

The tumor cells were maintained in tissue culture in minimum essential medium (MEM) supplemented with 5 or 10% fetal bovine serum (FBS), sodium pyruvate, nonessential amino acids, L-glutamine, and 2-fold vitamin solution (Gibco, Grand Island, N.Y.). The cultures were maintained on plastic and incubated in 5% CO₂-95% air at 37°C in a humidified incubator. All cultures were free of Mycoplasma and the following murine viruses: reovirus type 3; pneumonia virus; K virus; Theiler's encephalitis virus; Sendai Virus; minute virus; mouse adenovirus; mouse hepatitis virus; lymphocytic choriomeningitis virus; ectromelia virus; lactate dehydrogenase virus (all assayed by MA Bioproducts, Walkersville, MD). 29 The Agarose cultures used in the assays were prepared as follows: Agarose (Sigma Chemical Co. St. Louis, MO) was dissolved in distilled water and autoclaved at 120°C for 20 min. MEM with 10% FBS and 0.6% agarose was plated in 30-mm-diameter plastic dishes to provide a base layer (1 mL per dish). Suspensions of breast carcinoma cells were filtered through 20 mm Nitex nylon mesh (Tetko, Elmsford, N.Y.) to remove any clumps of cells and then mixed with MEM containing 10% FBS (20% FBS for cultures of MDA-MB-361 cells) and different concentrations of agarose. This mixture was overlaid on the base layers. The cell

3 4 number per dish in 1.5 mL was 5 X 10 for cultures of 0.3 and 0.6% agarose, 10 cells

4 in 0.9% agarose, and 2 X 10 cells in 1.2% agarose. The culture dishes were incubated at 37°C in a humidified incubator in a 5% CO₂-95% air atmosphere. The numbers and diameters of tumor colonies examined 30 days after plating were determined using a microscope equipped with a Filar micrometer (Cambridge Instruments, Deer Lake, IL). The MDA-MB-435 inhibition of colony formation in agarose assay was carried out as follows: Cells were incubated for 1 h at 37°C in the presence of compound at 0.6 to 10 mM, then mixed with agarose to achieve a final concentration of 0.3 or 0.9% and plated in 35 mm wells. Colonies of diameter greater than 50 μm were counted at 14 days (0.3% agarose) of 21-25 days (0.9% agarose). Percent inhibition was calculated by comparison with colony numbers in control cultures (cells incubated with medium alone).

The TXM-13 inhibition of colony formation in agarose test was carried out as follows. TXM-13 human melanoma cells were plated in agarose following incubation for one hour with the compounds at 0.6 to 10 mM. The assays for activity of compounds #9 and #10 produced low colony numbers in control and test groups

3 . 4

(inoculum of 5 X 10 per dish in 0.3% agarose and 10 per dish in 0.9% agarose). Cell inoculum was increased (x 2) for the other experiments, producing larger colony numbers. Colony numbers were counted on day 21 - 25 after plating. 30 Table III Partial summary of testing of the synthetic structural analogs of glycoamines.

Compound Murine cancer, Murine cancer, Human cancer, number in vitro assay in vivo assay in vitro assay

1 2 3 4 5 6 7 8 9

SSGA-1 ++ ++ - + ++ ++ ++

SSGA-2 ++ + - 0 0 ++ ++

SSGA-3 ++ ++ ++ 0 ++ ++ ++

SSGA-4 ++ - - 0

SSGA-5 ++ ~ - + 0 0

SSGA-6 ++ - - 0 0

SSGA-7 0 ++

SSGA-8 0 ++ + 0

SSGA-9 - - ++ + 0 ++ 0 0

SSGA- 10 - ++ ++ + ++ ++ 0

SSGA-11 ++

SSGA-12 + + + ++ ++ ++ ++ ++

SSGA- 13 ++ ++ + ++ ++ ++ ++ ++ ++

SSGA-14 ++ - + + ++

SSGA- 15 0 0 + 0

SSGA-16 ++ 0 0 ++ ++

SSGA- 17 ++ - ++ ++

SSGA- 18 ++ ++ 0

SSGA-19 + ++ + ++ ++ ++ ++ ++

SSGA-20 ++ + ++

SSGA-21 ++ 0

SSGA-22 ++ 0 ~

SSGA-23 ++ ~ -

SSGA-24 ~ - ++ 0

SSGA-25 0 0 +

SSGA-26 - 0 +

31

SSGA-27 ~ 0 +

SSGA-28 0 0 +

SSGA-29 — 0 +

SSGA-30 — 0 -H-

SSGA-31 0 ++

SSGA-32 0 +

SSGA-33 + ++

SSGA-34 - ++

SSGA-35 0 ++ ++

SSGA-36 + ++ + ++

SSGA-37 + -

SSGA-38 0 +

SSGA-39 -

SSGA-40 +

SSGA-41 +

SSGA-42 +

SSGA-43 +

SSGA-44 +

SSGA-45 +

SSGA-46 +

SSGA-47 +

SSGA-48 +

SSGA-49 +

SSGA-50 +

SSGA-51 +

SSGA-52 +

SSGA-53 +

SSGA-54 +

SSGA-55 0

32

Test Num.

1 MX-induced fibrosarcoma, in vitro cell aggregation assay;

2 3LL (Lewis) carcinoma, in vitro cell aggregation assay;

3 B 16 melanoma, in vitro cell aggregation assay;

4 F10 B 16 melanoma metastatic cell line, in vitro cell aggregation assay;

5 MX-induced fibrosarcoma, in vivo experimental metastasis assay;

6 3LL (Lewis) carcinoma, in vivo experimental metastasis assay;

7 B16 melanoma, in vivo experimental metastasis assay;

8 MDA-MB-435 human breast carcinoma metastatic cell line, in vitro colony formation in agarose assay;

9 TXM-13 human melanoma metastatic cell line, in vitro colony formation in agarose assay;

Result

+ Inhibition

++ Strong Inhibition (>50%)

Stimulation

Strong Stimulation (>50%) 0 No effect

33 The results of the above three classes of assays are summarized in Table III. It should be noted that, with the exception of SSGA-55 which was only examined in one test, all of the compounds either promote or inhibit cell adhesion in at least one test. These data suggest that the class of compounds described in the present invention are all affectors of cell adhesion. Some compounds, such as SSGA-12, SSGA- 13, SSGA-36 and SSGA-19 inhibit cell aggregation in every test in which they were examined suggesting that these compounds are "universal" inhibitors. Other compounds exhibit different effects depending on the cell type and assay suggesting that these compounds are cell type specific in their inhibition or promotion of cell adhesion. The effect of synthetic glycoamines also was tested in vivo using a model of human cancer metastasis in nude mice. A model of spontaneous human breast cancer metastasis to the lungs following orthotopic implantation of MDA-MB- 435 cells in nude mouse m.f.p. was used for evaluation of antimetastatic activity of synthetic glycoamines. Three synthetic glycoamines, SSGA 12, SSGA 13 and SSGA 19, were tested in vivo using the protocol described below. These three compounds demonstrate the activity of L and D configurations of amino acids as well as compounds including monosaccharides and disaccharides. Each of these compounds was shown to inhibit colony formation by MDA-MB-435 cells in dense agarose gel as shown in Test 8 described above and summarized in Table III and Fig. 3. Two treatment schedules were designed based on the behavior of

MDA-MB-435 m.f.p. tumors. Spontaneous metastasis from MDA-MB-435 m.f.p. tumors occurs as a function of both time and tumor size. When tumors are removed at 5 mm diameter after 4 weeks, the incidence of lung metastasis is 30 percent. The incident rate increases to 75 percent when the tumors are removed at 10 mm and to 100 percent when tumors are allowed to reach 15 mm before resection (Zhang, et al., "Relative malignant potential of human breast carcinoma cell lines established from pleural effusions and a brain metastasis," Invasion & Metastasis 11 :204-215, 1991, and Price, et al., "Tumorigenicity and metastasis of human breast carcinoma cell lines in nude mice," Cancer Res., 50:717-721, 1990). This data suggests that tumor cells are disseminating from the m.f.p. tumors over a long period of time. 34 Based on this observation two nude mouse - human breast cancer xenograft experimental treatment protocols were used to determine in vivo activity of synthetic glycoamines. Mice in group A (metastasis chemoprevention protocol), were treated intra peritoneally (i.p.) daily from two days after tumor cell injection until the end of the experiment (17 weeks). For mice in group B (micrometastasis therapy protocol), daily i.p. treatment started when the mean tumor diameter was 10 mm. After seven days of treatment, the primary tumors were removed, and the mice were treated for a further four weeks (a total of five weeks of treatment.)

Daily treatment with synthetic glycoamines caused a significant reduction in both the incidence and number of spontaneous pulmonary metastases of MDA-MB-435 human breast carcinoma. The antimetastatic activity of synthetic glycoamines was detected in both experimental treatment protocols. As shown in Figs. 4a and 4b, only 18 to 22 percent of control mice (4 of 18 control mice in group A and 3 of 17 control mice in group B) failed to develop pulmonary metastases. In contrast, 83 to 57 percent of mice treated with SSGA 13 (5 of 6 treated mice in group A and 4 of 7 treated mice in group B) and 71 to 67 percent of mice treated with SSGA 19 (5 of 7 treated mice in group A and 4 of 6 treated mice in group B) failed to develop pulmonary metastasis. Of all treated mice in group A, the incidence of metastasis was decreased 4.6 fold in mice treated with SSGA 13 and 2.7 fold in mice treated with SSGA 19. As shown in Table IV, the average number of spontaneous pulmonary metastases was reduced from 37 in control mice to 0.2 for SSGA 13 and 0.9 for SSGA 19 in treated mice in group A. A similar trend toward inhibition of the number of pulmonary metastasis in treated mice in group B was noticed in mice treated with SSGA 13 and SSGA 19.

35 Table IV

Spontaneous Lung Metastasis of MDA-MB-435 Human Breast Carcinoma in Nude Mice Treated with Synthetic Glycoamines

Treatment Lung Metastasis Number

Group A Group B

Control 37(0-150) 32(0-150)

SSGA-13 0.2(0-1) 22(0-100)

SSGA-19 0.9(0-5) 8(0-40)

SSGA-12 39(0-150) 37(0-150)

Medium number (and range) of lung metastases. Metastasis scored both macroscopically and microscopically.

36

As described above, a common mechanism of biological activity among synthetic glycoamines as a class is the inhibition of cell aggregation and adhesion. In addition to the inhibition of β-galactoside-mediated homotypic cancer cell aggregation, another potential mechanism for the antimetastatic activity of synthetic glycoamines may include induction of apoptosis.

Synthetic glycoamines were shown to induce in target cells the genetic cell suicide program known as programmed cell death or apoptosis. Three types of assay were employed to document the induction of apoptosis in target cells by synthetic glycoamines: the viability assay, the TUNEL assay, and DNA fragmentation analysis.

Cells were harvested from subconfluent cultures, washed three times in warm serum-free medium and resuspended at the following concentrations: 60,000 cells per mL in medium containing 10 percent fetal calf serum, 200,000 cells per mL in medium containing 1 percent fetal calf serum, and 200,000 cells per mL in medium containing 0.1 percent fetal calf serum. 2 mM or 5mM synthetic glycoamines were added at time zero. Cells were plated at low density in multiple 25 cm (5 mL cell suspension per flask) or 75 cm (15 mL cell suspension per flask) flasks. Once daily for six days after plating, the cells were harvested from the cultures and the viable cell number per plate was determined by staining with trypan blue or acridine orange. The assessment of cell cultures for viable and for apoptotic cells by acridine orange staining was performed using chromating condensation, nuclear fragmentation, and cellular shrinkage as criteria of the process of apoptosis. Cells were stained with acridine orange (5 μg mL^" , Molecular Probes, Eugene, OR) and observed by fluorescence microscopy. The percentage of viable versus apoptotic cells was determined from counts on at least 200 cells per individual culture flask with triplicate cultures sampled at each time point. Average deviation between triplicates usually is less than 5 percent. Treatment with synthetic glycoamines resulted in significant loss of viability of target cells at 48 hours after treatment.

Identification of apoptotic cells was performed employing the TUNEL method (terminal deoxynucleotidyl transferase-mediated dUTP-X nick end labeling method). Cells were prepared as described above in the viability assay. The In Situ 37

Cell Death Detection Kit, POD (Boehringer Mannheim Co., Indianapolis, IN), which uses an anti-fluorescein antibody conjugated to a peroxidase reporter molecule as the detection reagent, was employed. In addition to its effect on cell aggregation shown in Fig. 5, treatment of MDA-MB435 cells with synthetic glycoamines caused a 4 to 6 fold increase in the apoptosis level (Fig. 6A).

In the DNA fragmentation assay, cell lines were plated in flasks and treated as described for the viability assay. The cells were trypsinized and harvested by low-speed centrifugation at various time points to combine floating cells with the attached cells. Low molecular weight DNA was isolated as described in Glinsky, GN. and Glinsky, V.V., "Apoptosis and metastasis: A superior resistance of metastatic cancer cells to programmed cell death." Cancer Letters, 101:43-51 (1996). The cells were lysed in neutral lysing solution (0.5% Triton X-100, 10 mM EDTA, and 10 mM Tris, pH 7.4) containing 100 mg of proteinase K (Sigma Chemical Co., St. Louis, MO) per mL (100 mL per lxlO⁶ cells) for 1 hour at 37°C. The DΝA was then extracted three times with phenol and chloroform:isoamyl alcohol (24: 1).

Following the first phenol-chloroform extraction, the high molecular weight DΝA was removed by centrifugation for 25 minutes at 16,000 x g at 4°C. In selected experiments, RΝAse digestion, using 200 μg of pancreatic RΝAse A (Sigma) per mL, was performed prior to the agarose gel electrophoresis of the DΝA samples. Equal volumes of Hirt supernatant fractions from metastatic cell lines were analyzed by electrophoresis in a 1.2% agarose gel and visualized by ethidium bromide staining. Appearance of low-molecular weight DΝA in the Hirt supernatant was used as an indication of the induction of DΝA fragmentation and apoptosis. As shown in Fig. 6b, the DΝA fragmentation analysis clearly demonstrated an accumulation of low molecular weight apoptotic DΝA in MDA-MB-435 cells at 48 hours after treatment with synthetic glycoamines.

Application Of Synthetic Glycoamines In Combination With Standard Anticancer Agents And/Or Standard Methods Of Cancer Therapy As shown in Figs. 4a, 4b and Table IV, synthetic glycoamines significantly enhance the efficacy of the most common method of anticancer therapy, surgical removal of primary tumors. The incidence of metastatic dissemination in 38 mice treated with a combination of daily intraperitoneal injections of synthetic glycoamines and surgical removal of primary tumors was decreased -3-5 fold compared to mice treated with surgery alone.

Application of synthetic glycoamines in combination with standard anticancer agents and/or standard methods of cancer therapy also increases the effectiveness of other anticancer treatments. Combination cancer therapy with synthetic glycoamines achieves significant inhibition of clonogenic growth of cancer cells at substantially lower doses of cytotoxic drugs. The synergistic anticancer effect of synthetic glycoamines and chemotherapeutic drugs will permit a patient to tolerate for a longer period of time the dose of chemotherapy that still causes an efficient killing of cancer cells thus improving the clinical efficacy of cancer treatment. Therefore, the major potential advantages of the methods of combination cancer therapy of the present invention are: i) the ability to decrease the required dose of chemotherapy and still achieve the efficient killing of cancer cells at substantially lower doses of cytotoxic agents which will lead to lower toxicity and decreased likelihood of development of adverse toxic reactions and complications; ii) at standard dose of chemotherapy, the ability to maintain longer the clinically efficient dose of chemotherapeutic drug, which will allow a substantially larger fraction of cancer cells to enter the drug-sensitive phase of the cell cycle and become a target for cytotoxic agents; ii) the ability to achieve the efficient killing of cancer cells at substantially lower doses of cytotoxic agents, which will improve the efficacy of anticancer treatment in patients and/or parts of the body with adverse pharmacokinetic and poor drug bioavailability; and iv) the application of the synergistic combination of anticancer drugs employing different molecular mechanisms of apoptosis induction, which will significantly decrease the likelihood of drug resistance development.

Combination therapy experiments employing synthetic glycoamines and standard chemotherapeutic agents such as Taxol, cisplatin, and doxorubicin were performed in vitro utilizing a clonogenic growth assay. 39 Clonogenic growth assay. Clonogenic growth assays utilizing several established human cancer cell lines were performed as follows. Cancer cell lines were maintained as monolayer cultures in growth medium containing RPMI 1640 supplemented with 2 mM L-glutamine, 100 μg/ml gentamicin, and 10% prescreened fetal calf serum (FCS). The cultures were maintained on plastic and incubated in 5% CO₂/95% air at 37°C in a humidified incubator. Tumor cells were harvested from subconfluent cultures (50-70% confluence) by rinsing the monolayer with a 0.25% trypsin/0.02% EDTA solution. After 1 minute, the flask was tapped to dislodge the cells, serum-supplemented medium was added, and the suspension pipetted to produce a single-cell suspension. The live cell counts were obtained by Trypan blue dye exclusion assay. Cells were resuspended in growth medium and plated at low density in quadruplicate (200 viable cells per well in a 24-well culture plate) without (control samples) and with additional compounds that were tested. Five to seven days later, the cells were fixed with 1% formaldehyde in PBS, stained with hematoxylin, and colonies of more than 20 cells were scored. Colony forming efficiency (CFE) was then determined as the ratio of the number of colonies/number of cells plated. The surviving fraction of cells was calculated as the ratio of the CFE of the drug-treated culture and the CFE of the nontreated control culture. Synthetic glycoamine analogues alone were capable to significantly inhibit clonogenic growth of many different human cancer cell lines. As shown in Figs. 7 and 12 and Table V, in most cases we were able to achieve a 100% inhibition of clonogenic growth of human cancer cells by synthetic glycoamines. Inhibition doses listed in Table V were derived from dose response curves obtained for each compound. It should be noted that all of the tested compounds inhibit clonogenic growth of several different human cancer cell lines, suggesting that the class of molecules described in the present invention is the "universal" inhibitor of clonogenic growth potential of malignant cells. 40

Table V

Inhibition of Clonogenic Growth of Human Cancer Cells by Synthetic Glycoamines

Inhibition Dose Inhibition Dose M

Compound mM >90% 50% Type of Cancer Number

SSGA-13 2 0.8

SSGA-19 1 0.18

SSGA-36 0.31

SSGA-56 0.36

SSGA-57 0.31

SSGA-58 0.63

SSGA-13 2.5 2

SSGA-19 2.5 2

SSGA-13 0.9 3

SSGA-19 0.86 3

SSGA-13 0.87 4

SSGA-19 0.42 4

SSGA-1 2.5 0.782 4

SSGA-2 1.25 0.391 4

SSGA-3 0.312 0.098 4

SSGA-4 0.625 0.156 4

SSGA-5 0.625 0.156 4

SSGA-7 >1.25 0.86 4

SSGA-9 0.625 0.391 4

SSGA-11 0.039 <0.0049 4

SSGA-12 0.625 0.392 4

SSGA-13 0.312 0.078 4

SSGA-19 0.312 0.117 4

SSGA-33 0.625 0.156 4

SSGA-36 0.312 0.117 4

SSGA-50 0.039 0.0097 4

SSGA-51 0.312 <0.156 4

SSGA-56 0.375 0.094 4

SSGA-57 0.625 0.273 4

SSGA-61 0.078 0.0146 4

SSGA-62 0.156 0.039 4

SSGA-68 0.312 0.034 4

SSGA-80 1.25 0.411 4

SSGA-1 >2.5 1.88 5

SSGA-2 >2.5 1.64 5

SSGA-3 2.5 1.07 5

SSGA-4 1.25 0.49 5

SSGA-5 2.5 0.95 5 41

Inhibition Dose Inhibition Dose mM

Compound mM >90% 50% Type of Cancer Number

SSGA-6 >2.5 2.91 5

SSGA-8 >2.5 8.3 5

SSGA-9 2.5 0.94 5

SSGA-10 >2.5 1.79 5

SSGA-11 0.313 0.15 5

SSGA-12 2.5 0.94 5

SSGA-13 2.5 0.79 5

SSGA-14 2.5 0.47 5

SSGA- 15 2.5 0.74 5

SSGA-16 2.5 1.18 5

SSGA-19 1 0.33 5

SSGA-32 2.5 1.09 5

SSGA-39 >2.5 2.5 5

SSGA-40 1.25 0.512 5

SSGA-44 1.25 0.69 5

SSGA-46 >2.5 1.81 5

SSGA-50 0.23 0.094 5

SSGA-51 1.25 0.28 5

SSGA-59 1.25 0.68 5.

SSGA-60 >2.5 2.55 5

SSGA-61 0.156 0.087 5

SSGA-62 0.313 0.094 5

SSGA-63 0.313 0.113 5

SSGA-64 2.5 1.33 5

SSGA-65 >2.5 3.2 5

SSGA-66 1.25 0.69 5

SSGA-67 2.5 0.59 5

SSGA-68 0.625 0.19 5

SSGA-69 2.5 1 5

1 -highly metastatic human prostate carcinoma PC3MLN4

2-human prostate carcinoma PC3M

3 -human colon carcinoma Colo205

4-highly metastatic human breast carcinoma MDA-MB-435

5-human prostate carcinoma DU145

NOTE: Sensitivity of cancer cells to the inhibitory action of synthetic glycoamines was reduced after treatment with trypsin. Consequently, in most clonogenic growth experiments we utilized a non-enzymatic cell dissociation solution C-5914 (Sigma, StLouis, MO). 42 Combination Therapy Experiments. Four antimetastatic synthetic glycoamines, SSGA-13, SSGA-19, SSGA-70 and SSGA-72, and three well established potent antineoplastic agents, cisplatin, Taxol, and doxorubicin, were employed in combination therapy experiments utilizing clonogenic growth assays as described above. The antineoplastic agents chosen demonstrate that these agents and others that work by similar mechanisms can be used effectively in combination with synthetic glycoamines in the present invention. According to the present invention, any agents, methods, or other means that are applied as cancer therapies and work by a mechanism similar to the tested compounds can be used more effectively in combination with synthetic glycoamines. The compounds were tested in doses that caused a little or no effect on clonogenic growth of a given cancer cell line when the compound was applied alone. In one set of experiments, SSGA-13 and SSGA-19 were applied at 0.2 mM final concentration alone and in combination simultaneously with Taxol at 0.2 nM concentration or cisplatin at 0.0006 μg/ml to highly metastatic human breast carcinoma cell line MDA-MB-435. As shown in Figs. 8a and 8b, the inhibition of clonogenic growth of human breast carcinoma cell line MDA-MB-435 was substantially higher when synthetic glycoamines were applied in combination with chemotherapeutic drugs compared to corresponding single therapy panels.

Glycoamines synthesized from amines other than amino acids also showed a synergistic effect when used in combination with known antineoplastic agents. In two separate experiments, SSGA-70 was applied at 0.01 mM final concentration with Taxol at a concentration of 0.22nM and with cis-platin at a concentration of 0.6 ng/ml. As shown in Figs. 13 and 14, in both experiments the inhibition of clonogenic growth of human breast carcinoma cell line MDA-MB-435 was substantially higher when synthetic glycoamines were applied in combination with chemotherapeutic drugs compared to corresponding single therapy panels. A similar experiment was carried out with SSGA 72 applied at 0.001 mM concentration with Taxol at a concentration of 0.88 nM. As shown in Fig. 15, again, the inhibition of clonogenic growth of the MDA-MB-435 cell line was dramatically higher with the addition of the synthetic glycoamine. 43 SSGA-19 also was tested using human colon carcinoma cell line Colo205. SSGA-19 was applied at 0.2 mM final concentration alone and in combination with cisplatin at 0.006 μg/ml or doxorubicin at 0.002 μg/ml. In each experiment SSGA-19 and the chemotherapeutic agent was applied simultaneously. As shown in Fig. 9, the inhibition of clonogenic growth of human colon carcinoma cell line Colo-205 was substantially higher when the synthetic glycoamine was applied in combination with chemotherapeutic drugs compared to corresponding single therapy panels.

In another set of combination therapy experiments using highly metastatic human breast carcinoma cell line MDA-MB-435, the synthetic glycoamines were added to the cell culture dishes simultaneously, prior to or after the application of chemotherapeutic drugs. SSGA-19 was applied at 0.3 mM final concentration and Taxol was applied at 0.2 nM final concentration. As shown in Fig. 10, the inhibition of clonogenic growth of human breast carcinoma cell line MDA- MB-435 was substantially higher in combination therapy panels regardless of variation in application time for synthetic glycoamines. (Numbers in parentheses refer to the day of drug administration.)

Dose response analyses also were conducted with synthetic glycoamines in combination and alone. Fig. 11 shows the results from clonogenic growth assays using DU145 human prostate carcinoma cells conducted with various concentrations of Taxol and with and without the addition of SSGA-19 at 0.2 mM final concentration. Fig. 12 shows the results from clonogenic growth assays using DU 145 human prostate carcinoma cells conducted with various concentrations of synthetic glycoamine analog SSGA-19 at the concentrations indicated. Fig. 16 shows the results from clonogenic growth assays using MDA-

MB-435 human breast carcinoma cells conducted with various concentrations of Taxol with and without the addition of SSGA-70 at 0.01 mM final concentration. Fig. 17 shows the results from clonogenic growth assays using MDA-MB-435 human breast carcinoma cells conducted with various concentrations of cis-platin with and without the addition of SSGA-70 at 0.01 mM final concentration. Fig. 18 shows the results from clonogenic growth assays using MDA-MB-435 human breast carcinoma 44 cells conducted with various concentrations of Taxol with and without the addition of

SSGA-72 at 0.001 mM final concentration.

Comparison of the Activity of Synthetic Glycoamines Comprising Amines Other Than Amino Acids Synthetic glycoamines (SSGA-70 through SSGA-79 in Tables 1 and 2) were synthesized and tested in several biological assays and their activities were compared to the activities of synthetic glycoamine analogs SSGA-13 and SSGA-19 in corresponding bioassays. Clonogenic growth assays with compounds SSGA-70 through SSGA-79 were performed as described above. As shown in Table VI, in most cases we were able to achieve a 100% inhibition of clonogenic growth of human cancer cells by synthetic glycoamines. Inhibition doses listed in Table VI were derived from dose response curves obtained for each compound. It should be noted that all of the tested compounds inhibit clonogenic growth of several different human cancer cell lines, suggesting that the class of molecules described in the present invention is the "universal" inhibitor of clonogenic growth potential of malignant cells.

45 Table VI

ϋihibit nDose, M

CompGuriti 50% Type of Cancer

> 7o

SSGA-70 0.0195 0.156

SSGA-71 0.0195 0.078

SSGA-72 0.0049 0.0195

SSGA-73 0.0146 0.078

SSGA-74 0.078 0.312

SSGA-75 <0.0049 <0.0049

SSGA-76 0.469 1.25

SSGA-77 0.625 2.5

SSGA-78 0.039 0.156

SSGA-79 0.039 0.234

SSGA-70 0.018 0.313 2

SSGA-71 0.014 0.078 2

SSGA-72 0.012 0.078 2

SSGA-73 0.081 0.156 2

SSGA-74 0.64 2.5 2

SSGA-75 0.014 0.039 2

SSGA-76 2.5 >2.5 2

SSGA-77 0.69 1.25 2

SSGA-78 0.313 0.625 2

SSGA-79 0.313 0.625 2

Fructose >2.5 >2.5 2

Lactose >2.5 >2.5 2

Fructose >5.0 >5.0 1

Lactose >5.0 >5.0 1

Highly Metastatic Human Breast Carcinoma MDA-MB-435 Human Prostate Carcinoma DU145

46 Fig. 19 shows dose response curves for fructose alone and three fructose-containing synthetic glycoamines, SSGA-13 (N-(l -Deoxy-D fructos- l-yl)-D-leucine), SSGA-75 (N-(l -Deoxy-D-fructos- l-yl)-p-toluidine), and SSGA-78 (1 -Deoxy-D-fructos- 1- ylamine). Fig. 20 shows dose response curves for lactose alone and three lactose- containing synthetic glycoamines, SSGA-19 (N-(l -Deoxy-D-lactulos- l-yl)-L-leucine), SSGA-70 (N,N^'-(l-Deoxy-D-lactulos-l-yl)-l,6-diaminohexane), and SSGA-71 (N-(l- Deoxy-D-lactulos-l-yl)-N-methylaniline). Apoptosis Induction Experiments

In apoptosis induction experiments cells were plated as described for clonogenic growth assay. Identification of apoptotic cells was performed after 48 hours of incubation employing the TUΝEL assay (terminal deoxynucleotidyl transferase-mediated dUTP-X nick and labeling). The In Smu Cell Death Detection Kit, POD (Boehringer Mannheim Co., Indianapolis, IN), which uses and anti- fluorescein antibody conjugated to a peroxidase reporter molecule as the detection reagent, was employed. Treatment of MDA-MB-435 human breast carcinoma cells with the novel glycoamine analog, SSGA-70, caused induction of apoptosis (Fig. 21). In combination therapy experiments, the SSGA-70 caused synergistic induction of apoptosis in target cancer cells when combined with cytotoxic anti-cancer drug Taxol (Fig. 21). Similarly, SSGA-19 when used in combination with Taxol caused synergistic induction of apoptosis in target cancer cells (Fig. 22). It should be noted that the doses of the compounds employed in combination therapy experiments were selected as such that did not induce significant apoptosis when each compound was applied alone. However, when compounds were applied in combination they caused over 80% induction of apoptosis in cancer cells (Figs. 21 and 22). Naturally Occurring Glycoamines

It should be noted that larger glycoamines that include an amino acid linked to a sugar by one of the above-described links have been isolated from the blood stream of patients with various cancers. These compounds have been investigated as physiological components of human and rodent blood serum that merit interest as potential tumor makers. The level of these substances is substantially increased in blood serum from humans and animals with different forms of malignant 47 solid tumors and leukemias. Structurally the glycoamines detected in blood represent carbohydrate-amino acid conjugates containing from 5 to 29 amino acids and from 1 to 17 carbohydrate residues. The chemical structure of glycoamines reveal mono-, di- and trisaccharides bound to the amino acids and assembled into higher molecular weight compounds via the formation of ester, Schiff base and Amadori product-type bonds with the involvement of the amino groups of amino acids and hydroxyl, aldehyde or keto groups of the carbohydrates. The function of these naturally occurring glycoamines has yet to be determined.

While large glycoamines have been detected in nature, the much simpler compounds of the present invention have not been detected in blood.

If the compounds of the present invention exist in blood, they are presumably at concentrations below the detection threshold which is approximately 1 μMolar.

The present invention is not to be limited in scope by the exemplified embodiments which are intended as illustrations of single aspects of the invention, and methods which are functionally equivalent are within the scope of the invention. Indeed, various modifications of the invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description and accompanying drawings. Such modifications are intended to fall within the scope of the appended claims. All references cited within the instant specification are hereby incorporated by reference in their entirety.

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Claims

50 WHAT IS CLAIMED IS: L A method of inhibition of growth of cancer cells comprising the step of bringing the cancer cells into contact with a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products, said compound being present in sufficient concentration to inhibit growth of said cells. 2. The method of Claim 1 wherein said carbohydrate is a monosaccharide; 3. The method of Claim 1 wherein said carbohydrate is a disaccharide. 4. The method of Claim 1 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 5. The method of Claim 1 wherein a reactive group of said carbohydrate is covalently modified. 6. The method of Claim 1 wherein a reactive group of said amine is covalently modified. 7. The method of Claim 1 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-αrabz^'no-hexulos-l-yl)-(S)-2-amino-3-(4- hydroxyphenyl)-propanoic acid, (S)-2-(l-Deoxy-D-αrα/ zΗo-hexulos-l-amino)-3-(indol-3- yl)-propanoic acid, N-(l-Deoxy-D-αrαbz^'«o-hexulos-l-yl)-(R)-2-amino-4- methylpentanoic acid, N-(l-Deoxy-D- rα/3/«o-hexulos-l-yl)-(SJ-2-aminopropanoic acid, N-(l-Deoxy-D-ara&z^'«o-hexulos-l-yl)-CS 2-amino-3-methylbutanoic acid, N-(l-Deoxy- 4-O-(β-D-galactopyranos- 1 -yl)-D-αrø&mo-hexulos- 1 -yl)-(SJ-2-amino-4-methylpentanoic acid, N-(l-Deoxy-D-αraόz^'no-hexulos-l-yl)-(S)-2-amino-3-hydroxypropanoic acid, N,N'- Di(l-deoxy-D-«ra3z^'«o-hexulos-l-yl)-(S)-2,6-diaminohexanoic acid, S -2-(l-Deoxy-D- Ωraδ o-hexulos-l-amino)-3-(lH-imidazol-4-yl)-propanoic acid, N,N-Di(l-deoxy-D- arabino-hexulos- 1 -yl)-aminoethanoic acid, N-( 1 -Deoxy-D-arabino-hexulos- 1 -y 1 )-(S)- 51 2amino-5-guanidinovaleric acid, N, N-Di(2-deoxy-D-arabino-hexulos- 1 -y 1 )-4- aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di( 1 -deoxy-D-arabino-hexulos- 1 -y 1 )-amino)-2-N-formylaminohexanoic acid, N- (1 -Deoxy-D-arabino-hexulos- l-yl)-(S)-2-amino-2-phenylethanoic acid, N-(l-Deoxy-D- arabino-hexulos-l-yl)-N-methylaminoethanoic acid, N-(l -Deoxy-D-arabino-hexulos- 1- yl)-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid, N-(l-Deoxy-D-αraό o-hexulos- 1 -yl)-(S)-2-amino-3-phenylpropanoic acid, (S)-2-( 1 -Deoxy-D-αrab o-hexulos- 1 -amino)- 3-(indol-3-yl)-propanoic acid, SJ-2-(l-Deoxy-D-αrøόz«ø-hexulos-l-amino)-3-(lH- imidazol-4-yl)-propanoic acid, N,N-Di(l-deoxy-D-αrabz^'«o-hexulos-l-yl)-aminoethanoic acid, N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )-(R)-2-amino- 4-methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l-deoxy-D- arabino-hexulos-l-yl)-amino)-2-N-formylaminohexanoic acid, and N-(l-Deoxy-D- arabino-hexulos- 1 -y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 8. The method of Claim 1 wherein said compound is chosen from the group consisting of NiN -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino- hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-lyxo-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 - yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-( 1 -Deoxy-D- arabino-hexulos- 1 -yl)-morpholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-butylamine; 1 - Deoxy-D-arabino-hexulos- 1 -ylamine; and (S)-6-( 1 -Deoxy-D-arabino-hexulos- 1 -amino)- 2-N-acetylaminohexanoic acid. 9. The method of Claim 1 wherein said compound is NiN -Di(l- deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino-hexulos-l-yl)-l,6-diaminohexane. 10. The method of Claim 1 wherein said compound is N-(l-Deoxy-D- arabino-hexulos- 1 -yl)-N-methylaniline. 11. A method of enhancing the efficacy of standard cancer therapy comprising the steps of: 52 a) administering a standard cancer therapy; and b) administering a therapeutic amount of a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products. 12. The method of Claim 11 wherein said carbohydrate is a monosaccharide; 13. The method of Claim 11 wherein said carbohydrate is a disaccharide. 14. The method of Claim 11 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 15. The method of Claim 11 wherein a reactive group of said carbohydrate is covalently modified. 16. The method of Claim 11 wherein a reactive group of said amine is covalently modified. 17. The method of Claim 11 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-arabz^'«o-hexulos-l-yl)-(S)-2-amino-3-(4- hydroxyphenyl)-propanoic acid, (S)-2-(l-Deoxy-D-αrabz^'«o-hexulos-l-amino)-3-(indol-3- yl)-propanoic acid, N-(l-Deoxy-D-«rαbz>zo-hexulos-l-yl)-(R)-2-amino-4- methylpentanoic acid, N-( 1 -Deoxy-D-βrαbz^'wø-hexulos- 1 -yl)-(S)-2-aminopropanoic acid, N-(l-Deoxy-D-βr bz^'«o-hexulos-l-yl)-CSJ-2-amino-3-methylbutanoic acid, N-(l-Deoxy- 4-O-(β-D-galactopyranos- 1 -yl)-D-αrøbz^'«o-hexulos- 1 -yl)-fSJ-2-amino-4-methylpentanoic acid, N-( 1 -Deoxy-D-αra/3z^'«o-hexulos- 1 -yl)-(S)-2-amino-3-hydroxypropanoic acid, N,N'- Di(l-deoxy-D-αra/3 o-hexulos-l-yl)-(S)-2,6-diaminohexanoic acid, (SJ-2-(l-Deoxy-D- αrabz z -hexulos-l-amino)-3-(lH-imidazol-4-yl)-propanoic acid, N,N-Di(l-deoxy-D- αrab ø-hexulos-l-yl)-aminoethanoic acid, N-(l -Deoxy-D-arabino-hexulos- l-yl)-(S)- 2amino-5-guanidinovaleric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4- aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos- 1 -y 1 )-3 -aminopropanoic acid, 53 (S)-6-(Di( 1 -deoxy-D-arabino-hexulos- 1 -y 1 )-amino)-2-N-formylaminohexanoic acid, N- (1 -Deoxy-D-arabino-hexulos- 1 -y 1 )-(S)-2-amino-2-phenylethanoic acid, N-( 1 -Deoxy-D- arabino-hexulos- 1 -y 1 )-N-methylaminoethanoic acid, N-( 1 -Deoxy-D-arabino-hexulos- 1 - y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acidN-( 1 -Deoxy-D-αrøb ø-hexulos- 1 - yl)-(S)-2-amino-3-phenylpropanoic acid, (S)-2-(l-Deoxy-D-«ra/3z^'«o-hexulos-l-amino)-3- (indol-3-yl)-propanoic acid, (S)-2-(l-Deoxy-D-αrα/3z^'« -hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di(l-deoxy-D-αrα( z^'Mθ-hexulos-l-yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos- 1 -y 1 )-3 -aminopropanoic acid, (S)-6-(Di( 1 -deoxy-D- arabino-hexulos-l-yl)-amino)-2-N-formylaminohexanoic acid, and N-(l-Deoxy-D- arabino-hexulos-l-yl)-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 18. The method of Claim 11 wherein said compound is chosen from the group consisting of NiN -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- methylaniline; N-( 1 -Deoxy-D-lyxo-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-morpholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 19. The method of Claim 11 wherein said compound is N,N -Di(l- deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 20. The method of Claim 11 wherein said compound is N-(l -Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 21. A method of combination cancer therapy comprising the steps of: a) administering a standard cancer therapy; and 54 b) administering a therapeutic amount of a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products. 22. The method of Claim 21 wherein said carbohydrate is a monosaccharide; 23. The method of Claim 21 wherein said carbohydrate is a disaccharide. 24. The method of Claim 21 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 25. The method of Claim 21 wherein a reactive group of said carbohydrate is covalently modified. 26. The method of Claim 21 wherein a reactive group of said amine is covalently modified. 27. The method of Claim 21 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D- rαr z^'no-hexulos-l-yl)-(S)-2-amino-3-(4- hydroxyphenyl)-propanoic acid, (S)-2-(l-Deoxy-D-αrabz^'«ø-hexulos-l-amino)-3-(indol-3- yl)-propanoic acid, N-( 1 -Deoxy-D-αr όz^'no-hexulos- 1 -yl)-(R)-2-amino-4- methylpentanoic acid, N-( 1 -Deoxy-D-αrøbz^'nø-hexulos- 1 -yl)- S -2-aminopropanoic acid, N-(l-Deoxy-D-βrα z zø-hexulos-l-yl)-(SJ-2-amino-3-methylbutanoic acid, N-(l-Deoxy- 4-0-(β-D-galactopyranos- 1 -yl)-D-αrabz«ø-hexulos- 1 -yl)-CS)-2-amino-4-methylpentanoic acid, N-(l-Deoxy-D-αrαbz^'«ø-hexulos-l-yl)-(S)-2-amino-3-hydroxypropanoic acid, N,N'- Di(l-deoxy-D-αrabmø-hexulos-l-yl)-(S)-2,6-diaminohexanoic acid, (S)-2-(l-Deoxy-D- rαbz^'πo-hexulos-l-amino)-3-(lH-imidazol-4-yl)-propanoic acid, N,N-Di(l-deoxy-D- αraσz^'«ø-hexulos-l-yl)-aminoethanoic acid, N-(l -Deoxy-D-arabino-hexulos- l-yl)-(S)- 2amino-5-guanidinovaleric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4- aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di( 1 -deoxy-D-arabino-hexulos- 1 -y 1 )-amino)-2-N-formylaminohexanoic acid, N- 55 (l-Deoxy-D-arabino-hexulos-l-yl)-(S)-2-amino-2-phenylethanoic acid, N-(l-Deoxy-D- arabino-hexulos- l-yl)-N-methylaminoethanoic acid, N-(l -Deoxy-D-arabino-hexulos- 1- y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acidN-( 1 -Deoxy-D- rab ø-hexulos- 1 - yl)-(5)-2-amino-3-phenylpropanoic acid, (S)-2-(l-Deoxy-D-αraσt«ø-hexulos-l-amino)-3- (indol-3-yl)-propanoic acid, (S)-2-(l-Deoxy-D-flra z^'«o-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di(l-deoxy-D-αrøbz^'«ø-hexulos-l-yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l-deoxy-D- arabino-hexulos- l-yl)-amino)-2-N-formylaminohexanoic acid, and N-(l-Deoxy-D- arabino-hexulos- 1 -y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 28. The method of Claim 21 wherein said compound is chosen from the group consisting of N,N -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- methylaniline; N-( 1 -Deoxy-D-lyxo-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-(l -Deoxy-D-arabino-hexulos- l-yl)-mo ho line; N-(l -Deoxy-D-arabino-hexulos- 1-yl)- butylamine; 1-Deoxy-D-arabino-hexulos-l-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 29. The method of Claim 21 wherein said compound is N,N -Di(l- deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 30. The method of Claim 21 wherein said compound is N-(l-Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 31. A method of inhibition of growth of cancer cells comprising the steps of: a) administering a standard cancer therapy; and 56 b) bringing the cancer cells into contact with a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products. 32. The method of Claim 31 wherein said carbohydrate is a monosaccharide; 33. The method of Claim 31 wherein said carbohydrate is a disaccharide. 34. The method of Claim 31 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 35. The method of Claim 31 wherein a reactive group of said carbohydrate is covalently modified. 36. The method of Claim 31 wherein a reactive group of said amine is covalently modified. 37. The method of Claim 31 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-αrab o-hexulos-l-yl)-(S)-2-amino-3-(4- hydroxyphenyl)-propanoic acid, (S)-2-(l-Deoxy-D-αrabtno-hexulos-l-amino)-3-(indol-3- yl)-propanoic acid, N-( 1 -Deoxy-D-αr σz^'wo-hexulos- 1 -yl)-(R)-2-amino-4- methylpentanoic acid, N-(l-Deoxy-D-αrα6z^'«o-hexulos-l-yl)-(S -2-aminopropanoic acid, N-(l-Deoxy-D-αraσz^'n -hexulos-l-yl)-CSJ-2-amino-3-methylbutanoic acid, N-(l-Deoxy- 4-O-(β-D-galactopyranos- 1 -yl)-D-αrøbz^'«o-hexulos- 1 -yl)-fSJ-2-amino-4-methylpentanoic acid, N-( 1 -Deoxy-D-αr & o-hexulos- 1 -yl)-(S)-2-amino-3-hydroxypropanoic acid, N,N'- Di(l-deoxy-D-αrabz^'no-hexulos-l-yl)-(S)-2,6-diaminohexanoic acid, (S)-2-(l-Deoxy-D- rαbz^'«o-hexulos-l-amino)-3-(lH-imidazol-4-yl)-propanoic acid, N,N-Di(l-deoxy-D- αrα/ z^'«o-hexulos-l-yl)-aminoethanoic acid, N-(l -Deoxy-D-arabino-hexulos- l-yl)-(S)- 2amino-5-guanidinovaleric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4- aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l -deoxy-D-arabino-hexulos- l-yl)-amino)-2-N-formylaminohexanoic acid, N- 57 (1 -Deoxy-D-arabino-hexulos- l-yl)-(S)-2-amino-2-phenylethanoic acid, N-(l-Deoxy-D- arabino-hexulos- l-yl)-N-methylaminoethanoic acid, N-( 1 -Deoxy-D-arabino-hexulos- 1- y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acidN-( 1 -Deoxy-D-αrabmo-hexulos- 1 - yl)-(S)-2-amino-3-phenylpropanoic acid, (S)-2-(l-Deoxy-D-flra/3t«o-hexulos-l-amino)-3- (indol-3-yl)-propanoic acid, (SJ-2-(l-Deoxy-D- rab o-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di(l-deoxy-D-αra&mo-hexulos-l-yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos- 1 -y 1 )-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l-deoxy-D- arabino-hexulos- 1 -y 1 )-amino)-2-N-formylaminohexanoic acid, and N-( 1 -Deoxy-D- arabino-hexulos- l-yl)-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 38. The method of Claim 31 wherein said compound is chosen from the group consisting of N,N -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- methylaniline; N-(l-Deoxy-D-lyxo-hexulos-l-yl)-N-methylaniline; N-(l-Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-morpholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 39. The method of Claim 31 wherein said compound is NiN -Di(l- deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 40. The method of Claim 31 wherein said compound is N-(l -Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 41. A method of inhibition of growth of metastatic cancer cells comprising the step of administering a therapeutic amount of a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products in sufficient concentration to inhibit cells from said cancer from forming secondary tumors. 58 42. The method of Claim 41 wherein said carbohydrate is a monosaccharide; 43. The method of Claim 41 wherein said carbohydrate is a disaccharide. 44. The method of Claim 41 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 45. The method of Claim 41 wherein a reactive group of said carbohydrate is covalently modified. 46. The method of Claim 41 wherein a reactive group of said amine is covalently modified. 47. The method of Claim 41 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-αraόz zø-hexulos-l-yl)-3-aminopropanoic acid, N- (l-Deoxy-D-αr bz^'no-hexulos-l-yl)-aminoethanoic acid, N-(l-Deoxy-D-αrøσz^'«ø-hexulos- l-yl)-fSJ-2-amino-3-phenylpropanoic acid, N-(l-Deoxy-D-αraόt«o-hexulos-l-yl)-4- aminobutanoic acid, N-(l-Deoxy-D-αrøσz^'raø-hexulos-l-yl)-6-aminohexanoic acid, N-(l- Deoxy-D-αrabz^'z7 -hexulos-l-yl)-(S)-2-amino-4-methylpentanoic acid, N-(l-Deoxy-D- αraόz^'wo-hexulos- 1 -yl)-(R)-2-amino-4-methylpentanoic acid, N-(l-Deoxy-D-/y o-hexulos- l-yl)-(S)-2-amino-4-methylpentanoic acid, N-( 1 -Deoxy-4-0-(β-D-galactopyranos- 1 -yl)-D- αrαb o-hexulos-l-yl)-CS)-2-amino-4methylpentanoic acid, 6-0-((S -2-pyrrolidine carboxyl)-D-glucose, and N-(l-Deoxy-4-0-(β-D-galactopyranos- l-yl)-D-arabino- hexulos- l-yl)-(S -2-amino-3-phenylpropanoic acidN-(l-Deoxy-D-αrabz^'no-hexulos-l-yl)- (S)-2-amino-3-phenylpropanoic acid, (<S)-2-(l-Deoxy-D-αrabz^'nø-hexulos-l-amino)-3- (indol-3-yl)-propanoic acid, S)-2-(l-Deoxy-D-<3rabzno-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di(l-deoxy-D-αrαz z^'no-hexulos-l-yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactopyranos-l -yl )-D-arabino-hexulos-l -y l)-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l -deoxy-D- 59 arabino-hexulos- 1 -y 1 )-amino)-2-N-formylaminohexanoic acid, and N-( 1 -Deoxy-D- arabino-hexulos- 1 -y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 48. The method of Claim 41 wherein said compound is chosen from the group consisting of N,N -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- methylaniline; N-(l-Deoxy-D-lyxo-hexulos-l-yl)-N-methylaniline; N-(l-Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-morpholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 49. The method of Claim 41 wherein said compound is N,N -Di( 1 - deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 50. The method of Claim 41 wherein said compound is N-(l-Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 51. A method of inhibition of growth of metastatic cancer cells comprising the steps of: a) administering a standard cancer therapy; and b) administering a therapeutic amount of a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products. 52. The method of Claim 51 wherein said carbohydrate is a monosaccharide; 53. The method of Claim 51 wherein said carbohydrate is a disaccharide. 54. The method of Claim 51 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 60 55. The method of Claim 51 wherein a reactive group of said carbohydrate is covalently modified. 56. The method of Claim 51 wherein a reactive group of said amine is covalently modified. 57. The method of Claim 51 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-αrabt«ø-hexulos-l-yl)-3-aminopropanoic acid, N- (l-Deoxy-D-αrab ø-hexulos-l-yl)-aminoethanoic acid, N-(l-Deoxy-D-αrab o-hexulos- l-yl)-fSJ-2-amino-3-phenylpropanoic acid, N-(l-Deoxy-D-αraøt«o-hexulos-l-yl)-4- aminobutanoic acid, N-(l-Deoxy-D-αrασz^'wø-hexulos-l-yl)-6-aminohexanoic acid, N-(l- Deoxy-D-σrαbwø-hexulos-l-yl)-(S)-2-amino-4-methylpentanoic acid, N-(l-Deoxy-D- αraø ø-hexulos-l-yl)-(R)-2-amino-4-methyιpentanoic acid, N-(l-Deoxy-D-/yxo-hexulos- l-yl)-(S)-2-amino-4-methylpentanoic acid, N-(l-Deoxy-4-0-(β-D-galactopyranos-l-yι)-D- αrαb ø-hexulos-l-yl)-fSJ-2-amino-4methylpentanoic acid, 6-O-(CS_y)-2-pyrrolidine carboxyl)-D-glucose, and N-(l-Deoxy-4-0-(β-D-galactopyranos- l-y\)- -arabino- hexulos- l-yl)-CS -2-amino-3-phenylpropanoic acidN-(l-Deoxy-D-αrab ø-hexulos-l-yl)- (S)-2-amino-3-phenylpropanoic acid, (S)-2-(l-Deoxy-D-αr σz^'no-hexulos-l-amino)-3- (indol-3-yl)-propanoic acid, CS)-2-(l-Deoxy-D-αra/3z^'nø-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di(l-deoxy-D-αrabmø-hexulos-l-yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactopyranos-l -yl)-D-arabino-hexulos-l-yl)-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos- 1 -y 1 )-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l-deoxy-D- arabino-hexulos- 1 -y 1 )-amino)-2-N-formylaminohexanoic acid, and N-( 1 -Deoxy-D- arabino-hexulos- 1 -y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 58. The method of Claim 51 wherein said compound is chosen from the group consisting of NiN -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- methylaniline; N-( 1 -Deoxy-D-lyxo-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; 61 N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-moφholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 59. The method of Claim 51 wherein said compound is NiN -Di(l - deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 60. The method of Claim 51 wherein said compound is N-(l -Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 61. A method of combination therapy of cancer metastasis comprising the steps of: a) administering a standard cancer therapy; and b) administering a therapeutic amount of a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products. 62. The method of Claim 61 wherein said carbohydrate is a monosaccharide; 63. The method of Claim 61 wherein said carbohydrate is a disaccharide. 64. The method of Claim 61 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 65. The method of Claim 61 wherein a reactive group of said carbohydrate is covalently modified. 66. The method of Claim 61 wherein a reactive group of said amine is covalently modified. 67. The method of Claim 61 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-αrασt«ø-hexulos-l-yl)-3-aminopropanoic acid, N- ( 1 -Deoxy-D-αrασzΗo-hexulos- 1 -yl)-aminoethanoic acid, N-( 1 -Deoxy-D-αrαbz^'πo-hexulos- l-yl)-(S)-2-amino-3-phenylpropanoic acid, N-(l-Deoxy-D-αrabz«ø-hexulos-l-yl)-4- 62 aminobutanoic acid, N-(l-Deoxy-D-αrab o-hexulos-l-yl)-6-aminohexanoic acid, N-(l- Deoxy-D-αraόt/io-hexulos-l-yl)-(S)-2-amino-4-methylpentanoic acid, N-(l-Deoxy-D- αrøbzno-hexulos-l-yl)-(R)-2-amino-4-methylpentanoic acid, N-(l-Deoxy-D-/yxo-hexulos- l-yl)-(S)-2-amino-4-methylpentanoic acid, N-(l-Deoxy-4-0-(β-D-galactopyranos-l-yl)-D- αrabz^'«o-hexulos-l-yl)-CSJ-2-amino-4methylpentanoic acid, 6-O-(CS_y)-2-pyrrolidine carboxyl)-D-glucose, and N-(l-Deoxy-4-0-(β-D-galactopyranos- l-yl)-D-αrαbz^'no- hexulos-l-yl)-CS_/)-2-amino-3-phenylpropanoic acidN-(l-Deoxy-D-αraZ?tn -hexulos-l-yl)- (S)-2-amino-3-phenylpropanoic acid, (S)-2-(l-Deoxy-D-αrabz>zo-hexulos-l-amino)-3- (indol-3-yl)-propanoic acid, CS -2-(l-Deoxy-D-αra/ z^'«o-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di( 1 -deoxy-D-αra/3z^'no-hexulos- 1 -yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l-deoxy-D- arabino-hexulos- l-yl)-amino)-2-N-formylaminohexanoic acid, and N-(l-Deoxy-D- arabino-hexulos-l-yl)-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 68. The method of Claim 61 wherein said compound is chosen from the group consisting of NiN -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- methylaniline; N-( 1 -Deoxy-D-lyxo-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-moφholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 69. The method of Claim 61 wherein said compound is NiN -Di(l- deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 70. The method of Claim 61 wherein said compound is N-(l-Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 63 71. A method of suppressing cancer metastasis comprising the step of administering a therapeutic amount of a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products, said compound being present in sufficient concentration to inhibit cells from said cancer from forming secondary tumors. 72. The method of Claim 71 wherein said carbohydrate is a monosaccharide; 73. The method of Claim 71 wherein said carbohydrate is a disacchari.de. 74. The method of Claim 71 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 75. The method of Claim 71 wherein a reactive group of said carbohydrate is covalently modified. 76. The method of Claim 71 wherein a reactive group of said amine is covalently modified. 77. The method of Claim 71 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-αraόz zo-hexulos-l-yl)-3-aminopropanoic acid, N- (1 -Deoxy-D-αr bz^'no-hexulos- 1 -yl)-aminoethanoic acid, N-( 1 -Deoxy-D-αraόz^'no-hexulos- 1 -yl)-(S^-2-amino-3-phenylpropanoic acid, N-( 1 -Deoxy-D-αrαό ø-hexulos-l-yl)-4- aminobutanoic acid, N-(l-Deoxy-D-αrαbmo-hexulos-l-yl)-6-aminohexanoic acid, N-(l- Deoxy-D- rαbz^'πo-hexulos-l-yl)-(S)-2-amino-4-methylpentanoic acid, N-(l-Deoxy-D- αrab -hexulos-l-yl)-(R)-2-amino-4-methylpentanoic acid, N-(l-Deoxy-D-/yxo-hexulos- l-yl)-(S)-2-amino-4-methylpentanoic acid, N-(l-Deoxy-4-0-(β-D-galactopyranos-l-yl)-D- αrα3z>zo-hexulos-l-yl)-(^'S -2-amino-4methylpentanoic acid, 6-O-(fS_y -2-pyrrolidine carboxyl)-D-glucose, and N-(l-Deoxy-4-0-(β-D-galactopyranos- \-y\)-D-arabino- hexulos- l-yl)-(S)-2-amino-3-phenylpropanoic acidN-(l-Deoxy-D-αrabz^'«o-hexulos-l-yl)- (S)-2-amino-3-phenylpropanoic acid, (S)-2-(l-Deoxy-D-αrαfo«ø-hexulos-l-amino)-3- 64 (indol-3-yl)-propanoic acid, CS)-2-(l-Deoxy-D-«rαb o-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di( 1 -deoxy-D-αrøbz>zo-hexulos- 1 -yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y l)-D-arabino-hexulos- 1 -y 1 )-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos- 1 -y 1 )-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l-deoxy-D- arabino-hexulos- l-yl)-amino)-2-N-formylaminohexanoic acid, and N-(l-Deoxy-D- arabino-hexulos-l-yl)-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 78. The method of Claim 71 wherein said compound is chosen from the group consisting of N,N -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- methylaniline; N-( 1 -Deoxy-D-lyxo-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-moφholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 79. The method of Claim 71 wherein said compound is N,N -Di(l- deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 80. The method of Claim 71 wherein said compound is N-(l-Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 81. A method of inducing apoptosis in target cells comprising the step of bringing said cells into contact with a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products, said compound being present in sufficient concentration to inhibit growth of said cells. 82. The method of Claim 81 wherein said carbohydrate is a monosaccharide; 83. The method of Claim 81 wherein said carbohydrate is a disaccharide. 65 84. The method of Claim 81 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 85. The method of Claim 81 wherein a reactive group of said carbohydrate is covalently modified. 86. The method of Claim 81 wherein a reactive group of said amine is covalently modified. 87. The method of Claim 81 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-<2røbz^'no-hexulos-l-yl)-(S)-2-amino-3-(4- hydroxyphenyl)-propanoic acid, (S)-2-( 1 -Deoxy-D-αra& o-hexulos- 1 -amino)-3-(indol-3- yl)-propanoic acid, N-( 1 -Deoxy-D-αrø&mø-hexulos- 1 -yl)-(R)-2-amino-4- methylpentanoic acid, N-(l-Deoxy-D-αrfl/3z«o-hexulos-l-yl)-CS -2-aminopropanoic acid, N-(l-Deoxy-D-αrα/3z^'«o-hexulos-l-yl)-CS -2-amino-3-methylbutanoic acid, N-(l-Deoxy- 4-0-(β-D-galactopyranos- 1 -yl)-D-αrabz^'«o-hexulos- 1 -yl)-fS -2-amino-4-methylpentanoic acid, N-( 1 -Deoxy-D-αrαbz^'no-hexulos- 1 -yl)-(S)-2-amino-3-hydroxypropanoic acid, N,N'- Di(l-deoxy-D-αrabz^'no-hexulos-l-yl)-(S)-2,6-diaminohexanoic acid, SJ-2-(l-Deoxy-D- αrαόz^'«o-hexulos-l-amino)-3-(lH-imidazol-4-yl)-propanoic acid, N,N-Di(l-deoxy-D- <3rα/ z^'«o-hexulos-l-yl)-aminoethanoic acid, N-(l -Deoxy-D-arabino-hexulos- l-yl)-(S)- 2amino-5-guanidinovaleric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4- aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l -deoxy-D-arabino-hexulos- l-yl)-amino)-2-N-formylaminohexanoic acid, N- (l-Deoxy-D-arabino-hexulos-l-yl)-(S)-2-amino-2-phenylethanoic acid, N-(l-Deoxy-D- arabino-hexulos- l-yl)-N-methylaminoethanoic acid, N-( 1 -Deoxy-D-arabino-hexulos- 1- y 1 )-(R)-2-amino-3 -(4-hydroxyphenyl)-propanoic acidN-( 1 -Deoxy-D-αrab o-hexulos- 1 - yl)-(S)-2-amino-3-phenylpropanoic acid, (S)-2-(l-Deoxy-D-αrabtno-hexulos-l-amino)-3- (indol-3-yl)-propanoic acid, CS -2-(l-Deoxy-D-«rabz zo-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di(l-deoxy-D-ara3z^'«o-hexulos-l-yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )-(R)-2-amino-4- 66 methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l-deoxy-D- arabino-hexulos- l-yl)-amino)-2-N-formylaminohexanoic acid, and N-(l-Deoxy-D- arabino-hexulos- 1 -y 1 )-(R)-2-amino-3 -(4-hydroxyphenyl)-propanoic acid. 88. The method of Claim 81 wherein said compound is chosen from the group consisting of NjN -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- methylaniline; N-( 1 -Deoxy-D-lyxo-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-moφholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 89. The method of Claim 81 wherein said compound is NiN -Di(l- deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 90. The method of Claim 81 wherein said compound is N-(l-Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 91. A method of induction of apoptosis in cancer cells comprising the steps of: a) administering a standard cancer therapy; and b) bringing cancer cells into contact with a compound comprising an amine said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products. 92. The method of Claim 91 wherein said carbohydrate is a monosaccharide; 93. The method of Claim 91 wherein said carbohydrate is a disaccharide. 94. The method of Claim 91 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, 67 galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 95. The method of Claim 91 wherein a reactive group of said carbohydrate is covalently modified. 96. The method of Claim 91 wherein a reactive group of said amine is covalently modified. 97. The method of Claim 91 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-αrα6z>zo-hexulos-l-yl)-(S)-2-amino-3-(4- hydroxyphenyl)-propanoic acid, (S)-2-( 1 -Deoxy-D-αraføΗø-hexulos- 1 -amino)-3-(indol-3- yl)-propanoic acid, N-( 1 -Deoxy-D-βrø& ø-hexulos- 1 -yl)-(R)-2-amino-4- methylpentanoic acid, N-(l-Deoxy-D-αrασz^'no-hexulos-l-yl)-(^'S -2-aminopropanoic acid, N-(l-Deoxy-D-αrabz>zo-hexulos-l-yl)-(^'S_/)-2-amino-3-methylbutanoic acid, N-(l-Deoxy- 4-O-(β-D-galactopyranos- 1 -yl)-D-αrabmø-hexulos- 1 -yl)-fS)-2-amino-4-methylpentanoic acid, N-(l-Deoxy-D-αr /3z«o-hexulos-l-yl)-(S)-2-amino-3-hydroxypropanoic acid, N,N'- Di(l-deoxy-D-αrαbz zo-hexulos-l-yl)-(S)-2,6-diaminohexanoic acid, fSJ-2-(l-Deoxy-D- αrøb ø-hexulos-l-amino)-3-(lH-imidazol-4-yl)-propanoic acid, N,N-Di(l-deoxy-D- αrøb ø-hexulos-l-yl)-aminoethanoic acid, N-(l -Deoxy-D-arabino-hexulos- l-yl)-(S)- 2amino-5-guanidinovaleric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4- aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos- 1 -y 1 )-3-aminopropanoic acid, (S)-6-(Di( 1 -deoxy-D-arabino-hexulos- 1 -y 1 )-amino)-2-N-formylaminohexanoic acid, N- (1 -Deoxy-D-arabino-hexulos- 1 -y 1 )-(S)-2-amino-2-phenylethanoic acid, N-( 1 -Deoxy-D- arabino-hexulos- 1 -y 1 )-N-methylaminoethanoic acid, N-( 1 -Deoxy-D-arabino-hexulos- 1 - y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acidN-( 1 -Deoxy-D-αr σ ø-hexulos- 1 - yl)-(S)-2-amino-3-phenylpropanoic acid, (S)-2-(l -Deoxy-D-αrασmø-hexulos- l-amino)-3- (indol-3-yl)-propanoic acid, (^'S_>)-2-(l-Deoxy-D-αrabz zo-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di( 1 -deoxy-D-αr όz^'«o-hexulos- 1 -yl)-aminoethanoic acid, N- (l-Deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino-hexulos-l-yl)-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l -deoxy-D- 68 arabino-hexulos- 1 -y 1 )-amino)-2-N-formylaminohexanoic acid, and N-( 1 -Deoxy-D- arabino-hexulos-l-yl)-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 98. The method of Claim 91 wherein said compound is chosen from the group consisting of NiN -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- methylaniline; N-( 1 -Deoxy-D-lyxo-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-moφholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 99. The method of Claim 91 wherein said compound is NiN -Di(l- deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 100. The method of Claim 91 wherein said compound is N-(l-Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 101. A method of inhibition of metastasis by inducing apoptosis in metastatic cancer cells comprising the step of administering a therapeutic amount of a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products, said compound being present in sufficient concentration to inhibit growth of said cells. 102. The method of Claim 101 wherein said carbohydrate is a monosaccharide; 103. The method of Claim 99 wherein said carbohydrate is a disaccharide. 104. The method of Claim 101 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 69 105. The method of Claim 101 wherein a reactive group of said carbohydrate is covalently modified. 106. The method of Claim 101 wherein a reactive group of said amine is covalently modified. 107. The method of Claim 101 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-αrab o-hexulos-l-yl)-(S)-2-amino-3-(4- hydroxyphenyl)-propanoic acid, (S)-2-(l-Deoxy-D-αrαøz^'nø-hexulos-l-amino)-3-(indol-3- yl)-propanoic acid, N-(l-Deoxy-D-αrøbt«ø-hexulos-l-yl)-(R)-2-amino-4- methylpentanoic acid, N-(l-Deoxy-D-αrαb/«ø-hexulos-l-yl)-(S)-2-aminopropanoic acid, N-(l-Deoxy-D-αrab ø-hexulos-l-yl)-(^'S)-2-amino-3-methylbutanoic acid, N-(l-Deoxy- 4-O-(β-D-galactopyranos- 1 -yl)-D-αraø ø-hexulos- 1 -yl)-CS -2-amino-4-methylpentanoic acid, N-(l-Deoxy-D-αrαbz>zø-hexulos-l-yl)-(S)-2-amino-3-hydroxypropanoic acid, N,N'- Di(l-deoxy-D-αrabz^'nø-hexulos-l-yl)-(S)-2,6-diaminohexanoic acid, S)-2-(l-Deoxy-D- αrαb/nø-hexulos-l-amino)-3-(lH-imidazol-4-yl)-propanoic acid, N,N-Di(l-deoxy-D- αrαbz^'wø-hexulos-l-yl)-aminoethanoic acid, N-(l-Deoxy-D-arabino-hexulos-l-yl)-(S)- 2amino-5-guanidinovaleric acid, N, N-Di(2-deoxy-D-arabino-hexulos- 1 -y 1 )-4- aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos- 1 -y 1 )-3-aminopropanoic acid, (S)-6-(Di(l -deoxy-D-arabino-hexulos- l-yl)-amino)-2-N-formylaminohexanoic acid, N- (1 -Deoxy-D-arabino-hexulos- 1 -y 1 )-(S)-2-amino-2-phenylethanoic acid, N-( 1 -Deoxy-D- arabino-hexulos- 1 -y 1 )-N-methylaminoethanoic acid, N-( 1 -Deoxy-D-arabino-hexulos- 1 - y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acidN-( 1 -Deoxy-D-αrabz^'«ø-hexulos- 1 - yl)-(S)-2-amino-3-phenylpropanoic acid, (S)-2-(l-Deoxy-D-αrαbz^'nø-hexulos-l-amino)-3- (indol-3-yl)-propanoic acid, (S -2-(l-Deoxy-D-αrab o-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di(l-deoxy-D-αrαøz^'nø-hexulos-l-yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactop) anos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l-deoxy-D- arabino-hexulos- 1 -y 1 )-amino)-2-N-formylaminohexanoic acid, and N-( 1 -Deoxy-D- arabino-hexulos-l-yl)-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 70 108. The method of Claim 101 wherein said compound is chosen from the group consisting of N_tN -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos-l-yl)-l,6-diaminohexane; N-(l-Deoxy-4-O-(β-D-galactopyranos-l-yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- methylaniline; N-(l-Deoxy-D-lyxo-hexulos-l-yl)-N-methylaniline; N-(l-Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-moφholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- 1 -amino)-2-N-acetylaminohexanoic acid. 109. The method of Claim 101 wherein said compound is N, N -Di( 1 - deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino-hexulos-l-yl)- 1,6-diaminohexane. 110. The method of Claim 101 wherein said compound is N-(l-Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 111. A method of suppressing cancer metastasis comprising the steps of: a) administering a standard cancer therapy; and b) administering a therapeutic amount of a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products. 112. The method of Claim 111 wherein said carbohydrate is a monosaccharide; 113. The method of Claim 111 wherein said carbohydrate is a disaccharide. 114. The method of Claim 111 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 115. The method of Claim 111 wherein a reactive group of said carbohydrate is covalently modified. 71 116. The method of Claim 111 wherein a reactive group of said amine is covalently modified. 117. The method of Claim 111 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-αrab o-hexulos-l-yl)-(S)-2-amino-3-(4- hydroxyphenyl)-propanoic acid, (S)-2-(l-Deoxy-D-αrabz^'«ø-hexulos-l-amino)-3-(indol-3- yl)-propanoic acid, N-(l-Deoxy-D-αrab ø-hexulos-l-yl)-(R)-2-amino-4- methylpentanoic acid, N-(l-Deoxy-D-Ωrασtnø-hexulos-l-yl)-CS)-2-aminopropanoic acid, N-(l-Deoxy-D-αrαb ø-hexulos-l-yl)-CS -2-amino-3-methylbutanoic acid, N-(l-Deoxy- 4-O-(β-D-galactopyranos- 1 -yl)-D-αrασz^'«ø-hexulos- 1 -yl)-f -2-amino-4-methylpentanoic acid, N-( 1 -Deoxy-D-αrαό o-hexulos- 1 -yl)-(S)-2-amino-3-hydroxypropanoic acid, N,N'- Di(l-deoxy-D-αra3 ø-hexulos-l-yl)-(S)-2,6-diaminohexanoic acid, fS,)-2-(l-Deoxy-D- αrαbz^'no-hexulos-l-amino)-3-(lH-imidazol-4-yl)-propanoic acid, N,N-Di(l-deoxy-D- αraøz^'«ø-hexulos-l-yl)-aminoethanoic acid, N-(l -Deoxy-D-arabino-hexulos- l-yl)-(S)- 2amino-5-guanidinovaleric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4- aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos- 1 -y 1 )-3-aminopropanoic acid, (S)-6-(Di(l -deoxy-D-arabino-hexulos- l-yl)-amino)-2-N-formylaminohexanoic acid, N- (l-Deoxy-D-arabino-hexulos-l-yl)-(S)-2-amino-2-phenylethanoic acid, N-(l-Deoxy-D- arabino-hexulos- 1 -y 1 )-N-methylaminoethanoic acid, N-( 1 -Deoxy-D-arabino-hexulos- 1 - yl)-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acidN-(l-Deoxy-D-αrασz zo-hexulos-l- yl)-(S)-2-amino-3-phenylpropanoic acid, (S)-2-(l-Deoxy-D-αraø ø-hexulos-l-amino)-3- (indol-3-yl)-propanoic acid, (^'S_/ -2-(l-Deoxy-D-αrabz^'nø-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di(l-deoxy-D-αraσt«ø-hexulos-l-yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l-deoxy-D- arabino-hexulos- 1 -y 1 )-amino)-2-N-formylaminohexanoic acid, and N-( 1 -Deoxy-D- arabino-hexulos- 1 -y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 118. The method of Claim 111 wherein said compound is chosen from the group consisting of NiN -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- 72 hexulos- l-yl)-l ,6-diaminohexane; N-(l-Deoxy-4-O-(β-D-galactopyranos-l-yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- methylaniline; N-( 1 -Deoxy-D-lyxo-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-moφholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 119. The method of Claim 111 wherein said compound is NiN -Di(l- deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 120. The method of Claim 111 wherein said compound is N-(l-Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 121. A method of combination therapy of cancer metastasis by inducing apoptosis comprising the steps of: a) administering a standard cancer therapy; and b) administering a therapeutic amount of a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products. 122. The method of Claim 121 wherein said carbohydrate is a monosaccharide; 123. The method of Claim 121 wherein said carbohydrate is a disaccharide. 124. The method of Claim 121 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 125. The method of Claim 121 wherein a reactive group of said carbohydrate is covalently modified. 126. The method of Claim 121 wherein a reactive group of said amine is covalently modified. 73 127. The method of Claim 121 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-αraσ ø-hexulos-l-yl)-(S)-2-amino-3-(4- hydroxyphenyl)-propanoic acid, (S)-2-(l-Deoxy-D-αraσ o-hexulos-l-amino)-3-(indol-3- yl)-propanoic acid, N-(l-Deoxy-D-αraσz^'«ø-hexulos-l-yl)-(R)-2-amino-4- methylpentanoic acid, N-( 1 -Deoxy-D-αrøσmø-hexulos- 1 -yl)-fS)-2-aminopropanoic acid, N-(l-Deoxy-D-αrαbznø-hexulos-l-yl)-(^'S)-2-amino-3-methylbutanoic acid, N-(l-Deoxy- 4-0-(β-D-galactopyranos- 1 -yl)-D-αrabz^'«ø-hexulos- 1 -yl)-(^-2-amino-4-methylpentanoic acid, N-( 1 -Deoxy-D-αrασmø-hexulos- 1 -yl)-(S)-2-amino-3-hydroxypropanoic acid, N,N'- Di(l-deoxy-D-αrαbwø-hexulos-l-yl)-(S)-2,6-diaminohexanoic acid, (5> -2-(l-Deoxy-D- αrabz^'«ø-hexulos-l-amino)-3-(lH-imidazol-4-yl)-propanoic acid, N,N-Di(l-deoxy-D- αrαøz^'«ø-hexulos-l-yl)-aminoethanoic acid, N-(l-Deoxy-D-arabino-hexulos-l-yl)-(S)- 2amino-5-guanidino valeric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4- aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l -deoxy-D-arabino-hexulos- l-yl)-amino)-2-N-formylaminohexanoic acid, N- (l-Deoxy-D-arabino-hexulos-l-yl)-(S)-2-amino-2-phenylethanoic acid, N-(l-Deoxy-D- arabino-hexulos- 1 -y 1 )-N-methylaminoethanoic acid, N-( 1 -Deoxy-D-arabino-hexulos- 1 - y 1 )-(R)-2-amino-3 -(4-hydroxyphenyl)-propanoic acidN-( 1 -Deoxy-D-αraσz^'«ø-hexulos- 1 - yl)-(S)-2-amino-3-phenylpropanoic acid, (S)-2-(l-Deoxy-D-αrab ø-hexulos-l-amino)-3- (indol-3-yl)-propanoic acid, CS -2-(l-Deoxy-D-αrabtnø-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di(l-deoxy-D-αrabz^'«ø-hexulos-l-yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos-l -y 1 )-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l-deoxy-D- arabino-hexulos-l-yl)-amino)-2-N-formylaminohexanoic acid, and N-(l-Deoxy-D- arabino-hexulos-l-yl)-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 128. The method of Claim 121 wherein said compound is chosen from the group consisting of NiN -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- 74 methylaniline; N-(l-Deoxy-D-lyxo-hexulos-l-yl)-N-methylaniline; N-(l-Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-moφholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 129. The method of Claim 121 wherein said compound is N,N -Di(l- deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 130. The method of Claim 121 wherein said compound is N-(l-Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 131. A method of suppressing cancer metastasis by inducing apoptosis comprising the steps of: a) administering a standard cancer therapy; and b) administering a therapeutic amount of a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products. 132. The method of Claim 131 wherein said carbohydrate is a monosaccharide; 133. The method of Claim 131 wherein said carbohydrate is a disaccharide. 134. The method of Claim 131 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 135. The method of Claim 131 wherein a reactive group of said carbohydrate is covalently modified. 136. The method of Claim 131 wherein a reactive group of said amine is covalently modified. 137. The method of Claim 131 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-αrαbz^'nø-hexulos-l-yl)-(S)-2-amino-3-(4- 75 hydroxyphenyl)-propanoic acid, (S)-2-(l-Deoxy-D-αra5z^'«o-hexulos-l-amino)-3-(indol-3- yl)-propanoic acid, N-( 1 -Deoxy-D-αraόz^'no-hexulos- 1 -yl)-(R)-2-amino-4- methylpentanoic acid, N-(l-Deoxy-D-αrαb o-hexulos-l-yl)-CS)-2-aminopropanoic acid, N-(l-Deoxy-D-αrαbz^'no-hexulos-l-yl)-CS -2-amino-3-methylbutanoic acid, N-(l-Deoxy- 4-O-(β-D-galactopyranos- 1 -yl)-D-αrabz^'«ø-hexulos- 1 -yl)- SJ-2-amino-4-methylpentanoic acid, N-(l-Deoxy-D-αrα/ z^'no-hexulos-l-yl)-(S)-2-amino-3-hydroxypropanoic acid, N,N'- Di(l-deoxy-D-αrα6z^'«o-hexulos-l-yl)-(S)-2,6-diaminohexanoic acid, (S)-2-(l-Deoxy-D- αrαbm -hexulos-l-amino)-3-(lH-imidazol-4-yl)-propanoic acid, N,N-Di(l-deoxy-D- αrαb -hexulos-1 -yl)-aminoethanoic acid, N-( 1 -Deoxy-D-arabino-hexulos- l-yl)-(S)- 2amino-5-guanidinovaleric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4- aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l -deoxy-D-arabino-hexulos- l-yl)-amino)-2-N-formylaminohexanoic acid, N- (l-Deoxy-D-arabino-hexulos-l-yl)-(S)-2-amino-2-phenylethanoic acid, N-(l-Deoxy-D- arabino-hexulos- 1 -y 1 )-N-methylaminoethanoic acid, N-( 1 -Deoxy-D-arabino-hexulos- 1 - y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acidN-( 1 -Deoxy-D-αrαbz^'«o-hexulos- 1 - yl)-(S)-2-amino-3-phenylpropanoic acid, (S)-2-(l-Deoxy-D-αra&z^'«o-hexulos-l-amino)-3- (indol-3-yl)-propanoic acid, CS)-2-(l-Deoxy-D-αrαδz zo-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di(l-deoxy-D-αrαδ o-hexulos-l-yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l-deoxy-D- arabino-hexulos- l-yl)-amino)-2-N-formylaminohexanoic acid, and N-(l-Deoxy-D- arabino-hexulos- 1 -y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 138. The method of Claim 131 wherein said compound is chosen from the group consisting of N,N ^'-Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- methylaniline; N-( 1 -Deoxy-D-lyxo-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; 76 N-(l -Deoxy-D-arabino-hexulos- l-yl)-moφholine; N-(l -Deoxy-D-arabino-hexulos- 1-yl)- butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 139. The method of Claim 131 wherein said compound is N_jN -Di(l- deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 140. The method of Claim 131 wherein said compound is N-(l-Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 141. A method of combination cancer therapy by inducing apoptosis in metastatic cancer cells comprising the steps of: a) administering a standard cancer therapy; and b) administering a therapeutic amount of a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products. 142. The method of Claim 141 wherein said carbohydrate is a monosaccharide; 143. The method of Claim 141 wherein said carbohydrate is a disaccharide. 144. The method of Claim 141 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfiructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 145. The method of Claim 141 wherein a reactive group of said carbohydrate is covalently modified. 146. The method of Claim 141 wherein a reactive group of said amine is covalently modified. 147. The method of Claim 141 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-αraόmo-hexulos-l-yl)-(S)-2-amino-3-(4- hydroxyphenyl)-propanoic acid, (S)-2-( 1 -Deoxy-D-αrab o-hexulos- 1 -amino)-3-(indol-3- yl)-propanoic acid, N-(l-Deoxy-D-αra/ z zσ-hexulos-l-yl)-(R)-2-amino-4- 77 methylpentanoic acid, N-(l-Deoxy-D-αrα/3tno-hexulos-l-yl)-(S_y -2-aminopropanoic acid, N-(l-Deoxy-D-αraδz^"«o-hexulos-l-yl)-CS)-2-amino-3-methylbutanoic acid, N-(l-Deoxy- 4-O-(β-D-galactopyranos- 1 -yl)-D-αrab o-hexulos- 1 -yl)-(SJ-2-amino-4-methylpentanoic acid, N-(l-Deoxy-D-αra/3tno-hexulos-l-yl)-(S)-2-amino-3-hydroxypropanoic acid, N,N'- Di(l-deoxy-D-αrαbz^'«o-hexulos-l-yl)-(S)-2,6-diaminohexanoic acid, (S)-2-(l-Deoxy-D- αrαb o-hexulos-l-amino)-3-(lH-imidazol-4-yl)-propanoic acid, N,N-Di(l-deoxy-D- αrαό o-hexulos-l-yl)-aminoethanoic acid, N-(l-Deoxy-D-arabino-hexulos-l-yl)-(S)- 2amino-5-guanidinovaleric acid, N, N-Di(2-deoxy-D-arabino-hexulos- 1 -y 1 )-4- aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di( 1 -deoxy-D-arabino-hexulos- 1 -y 1 )-amino)-2-N-formylaminohexanoic acid, N- (1 -Deoxy-D-arabino-hexulos- 1 -y 1 )-(S)-2-amino-2-phenylethanoic acid, N-( 1 -Deoxy-D- arabino-hexulos- 1 -y 1 )-N-methylaminoethanoic acid, N-( 1 -Deoxy-D-arabino-hexulos- 1 - y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acidN-( 1 -Deoxy-D-αrαήzwo-hexulos- 1 - yl)-(S)-2-amino-3-phenylpropanoic acid, (S)-2-(l-Deoxy-D-αrαbzΗ >-hexulos-l-amino)-3- (indol-3-yl)-propanoic acid, CS -2-(l-Deoxy-D-αrαbz^'no-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di(l-deoxy-D-αra6z^'no-hexulos-l-yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l-deoxy-D- arabino-hexulos- 1 -y 1 )-amino)-2-N-formylaminohexanoic acid, and N-( 1 -Deoxy-D- arabino-hexulos-l-yl)-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 148. The method of Claim 141 wherein said compound is chosen from the group consisting of NjN -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D- arabino-hexulos-l-yl)-N-methylaniline; N-(l-Deoxy-D-arabino-hexulos-l-yl)-N- methylaniline; N-(l-Deoxy-D-lyxo-hexulos-l-yl)-N-methylaniline; N-(l-Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-moφholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- 78 butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 149. The method of Claim 141 wherein said compound is N,N -Di(l- deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 150. The method of Claim 141 wherein said compound is N-(l-Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 151. A method of inhibition of growth of cancer by inducing apoptosis in cancer cells comprising the steps of: a) administering a standard cancer therapy; and b) administering a therapeutic amount of a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products. 152. The method of Claim 151 wherein said carbohydrate is a monosaccharide; 153. The method of Claim 151 wherein said carbohydrate is a disaccharide. 154. The method of Claim 151 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfhxctose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 155. The method of Claim 151 wherein a reactive group of said carbohydrate is covalently modified. 156. The method of Claim 151 wherein a reactive group of said amine is covalently modified. 157. The method of Claim 151 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-αrøό o-hexulos-l-yl)-(S)-2-amino-3-(4- hydroxyphenyl)-propanoic acid, (S)-2-(l-Deoxy-D-αrα/3z^'no-hexulos-l-amino)-3-(indol-3- yl)-propanoic acid, N-(l-Deoxy-D-αrα/ z«o-hexulos-l-yl)-(R)-2-amino-4- methylpentanoic acid, N-(l-Deoxy-D-αrαbz z -hexulos-l-yl)-CS)-2-aminopropanoic acid, 79 ^(l-Deoxy-D-αrα&tzzo-hexulos-l-y^-fS^^-amino-S-methylbutanoic acid, N-(l-Deoxy- 4-O-(β-D-galactopyranos-l-yl)-D-αrαbz^'«o-hexulos-l-yl)- S)-2-amino-4-methylpentanoic acid, N-(l-Deoxy-D-αrαό o-hexulos-l-yl)-(S)-2-amino-3-hydroxypropanoic acid, N,N'- Di(l-deoxy-D-αrαbz^'«o-hexulos-l-yl)-(S)-2,6-diaminohexanoic acid, (S)-2-(l-Deoxy-D- αrαbz zo-hexulos-l-amino)-3-(lH-imidazol-4-yl)-propanoic acid, N,N-Di(l-deoxy-D- αrαfø>zø-hexulos-l-yl)-aminoethanoic acid, N-(l-Deoxy-D-aτabino-hexulos-l-yl)-(S)- 2amino-5-guanidino valeric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4- aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos- 1 -y 1 )-3-aminopropanoic acid, (S)-6-(Di(l -deoxy-D-arabino-hexulos- l-yl)-amino)-2-N-formylaminohexanoic acid, N- (1 -Deoxy-D-arabino-hexulos- l-yl)-(S)-2-amino-2-phenylethanoic acid, N-(l-Deoxy-D- arabino-hexulos- l-yl)-N-methylaminoethanoic acid, N-(l -Deoxy-D-arabino-hexulos- 1- y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acidN-(l -Deoxy-D-αrafozzo-hexulos-l - yl)-(S)-2-amino-3-phenylpropanoic acid, (S)-2-(l-Deoxy-D-αrαbz^'«o-hexulos-l-amino)-3- (indol-3-yl)-propanoic acid, CS)-2-(l-Deoxy-D-αraό o-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di(l-deoxy-D-αra6z^'Hθ-hexulos-l-yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l-deoxy-D- arabino-hexulos- 1 -y 1 )-amino)-2-N-formylaminohexanoic acid, and N-( 1 -Deoxy-D- arabino-hexulos-l-yl)-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 158. The method of Claim 151 wherein said compound is chosen from the group consisting of N,N -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- methylaniline; N-(l-Deoxy-D-lyxo-hexulos-l-yl)-N-methylaniline; N-(l-Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-moφholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 80 159. The method of Claim 151 wherein said compound is N,N -Di(l - deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 160. The method of Claim 151 wherein said compound is N-( 1 -Deoxy- D-arabino-hexulos- 1 -yl)-N-methylaniline. 161. A method of inhibition of growth of cancer by inducing apoptosis in cancer cells comprising the step of administering a therapeutic amount of a compound comprising an amine, said amine being linked to a carbohydrate to form a compound chosen from the group consisting of Schiff bases, N-glycosides, and Amadori products, said compound being present in sufficient concentration to inhibit growth of said cells. 162. The method of Claim 161 wherein said carbohydrate is a monosaccharide; 163. The method of Claim 161 wherein said carbohydrate is a disaccharide. 164. The method of Claim 161 wherein said carbohydrate is chosen from the group consisting of arabinose, xylose, ribose, ribulose, fructose, deoxyfructose, galactose, glucose, rhamnose, mannose, tagatose, maltose, lactose, maltulose, and lactulose. 165. The method of Claim 161 wherein a reactive group of said carbohydrate is covalently modified. 166. The method of Claim 161 wherein a reactive group of said amine is covalently modified. 167. The method of Claim 161 wherein said compound is chosen from the group consisting of N-(l-Deoxy-D-αrabz^'«o-hexulos-l-yl)-(S)-2-amino-3-(4- hydroxyphenyl)-propanoic acid, (S)-2-(l-Deoxy-D-αrø&z^'«o-hexulos-l-amino)-3-(indol-3- yl)-propanoic acid, N-( 1 -Deoxy-D-αrαb o-hexulos- 1 -yl)-(R)-2-amino-4- methylpentanoic acid, N-( 1 -Deoxy-D-αrabz^'raø-hexulos- 1 -yl)-(SJ-2-aminopropanoic acid, N-(l-Deoxy-D-αra/>z zo-hexulos-l-yl)-('S)-2-amino-3-methylbutanoic acid, N-(l-Deoxy- 4-0-(β-D-galactopyranos- 1 -yl)-D-αrα o-hexulos- 1 -yl)-(S -2-amino-4-methylpentanoic acid, N-(l-Deoxy-D-αrαbz^'« -hexulos-l-yl)-(S)-2-amino-3-hydroxypropanoic acid, N,N'- 81 Di(l-deoxy-D-αrαbz^'no-hexulos-l-yl)-(S)-2,6-diaminohexanoic acid, (S)-2-(l-Deoxy-D- arabz^'no-hexulos-l-amino)-3-(lH-imidazol-4-yl)-propanoic acid, N,N-Di(l-deoxy-D- αrαb o-hexulos-l-yl)-aminoethanoic acid, N-(l-Deoxy-D-arabino-hexulos-l-yl)-(S)- 2amino-5-guanidinovaleric acid, N, N-Di(2-deoxy-D-arabino-hexulos- 1 -y 1 )-4- aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-6-(Di(l -deoxy-D-arabino-hexulos- l-yl)-amino)-2-N-formylaminohexanoic acid, N- (1 -Deoxy-D-arabino-hexulos- l-yl)-(S)-2-amino-2-phenylethanoic acid, N-(l-Deoxy-D- arabino-hexulos- l-yl)-N-methylaminoethanoic acid, N-( 1 -Deoxy-D-arabino-hexulos- 1- y 1 )-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acidN-( 1 -Deoxy-D-αrøbzΗo-hexulos- 1 - yl)-(S)-2-amino-3-phenylpropanoic acid, (S)-2-(l-Deoxy-D-αrabz^'«o-hexulos-l-amino)-3- (indol-3-yl)-propanoic acid, CS)-2-(l-Deoxy-D-αrabz^'no-hexulos-l-amino)-3-(lH-imidazol- 4-yl)-propanoic acid, N,N-Di( 1 -deoxy-D-αrαbz^'«o-hexulos- 1 -yl)-aminoethanoic acid, N- (1 -Deoxy-4-O-(β-D-galactopyranos- 1 -y 1 )-D-arabino-hexulos- 1 -y 1 )-(R)-2-amino-4- methylpentanoic acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-4-aminobutyric acid, N, N-Di(2-deoxy-D-arabino-hexulos-l-yl)-3-aminopropanoic acid, (S)-ό-(Di(l-deoxy-D- arabino-hexulos- l-yl)-amino)-2-N-formylaminohexanoic acid, and N-(l-Deoxy-D- arabino-hexulos-l-yl)-(R)-2-amino-3-(4-hydroxyphenyl)-propanoic acid. 168. The method of Claim 161 wherein said compound is chosen from the group consisting of NiN -Di(l-deoxy-4-O-(β-D-galactopyranos-l-yl)-D-arabino- hexulos- 1 -yl)- 1 ,6-diaminohexane; N-( 1 -Deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D- arabino-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-N- methylaniline; N-( 1 -Deoxy-D-lyxo-hexulos- 1 -yl)-N-methylaniline; N-( 1 -Deoxy-D- arabino-hexulos- 1 -yl)-piperidine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-4-methylaniline; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)-moφholine; N-( 1 -Deoxy-D-arabino-hexulos- 1 -yl)- butylamine; 1 -Deoxy-D-arabino-hexulos- 1-ylamine; and (S)-6-(l-Deoxy-D-arabino- hexulos- l-amino)-2-N-acetylaminohexanoic acid. 169. The method of Claim 161 wherein said compound is N,N -Di(l- deoxy-4-O-(β-D-galactopyranos- 1 -yl)-D-arabino-hexulos- 1 -yl)- 1 ,6-diaminohexane. 82 170. The method of Claim 161 wherein said compound is N-(l- Deoxy-D-arabino-hexulos- 1 -yl)-N-methylaniline.