CN109438461B - Tuliquiritigenin A derivative with anti-leukemia activity and preparation method and application thereof - Google Patents
Tuliquiritigenin A derivative with anti-leukemia activity and preparation method and application thereof Download PDFInfo
- Publication number
- CN109438461B CN109438461B CN201811168473.7A CN201811168473A CN109438461B CN 109438461 B CN109438461 B CN 109438461B CN 201811168473 A CN201811168473 A CN 201811168473A CN 109438461 B CN109438461 B CN 109438461B
- Authority
- CN
- China
- Prior art keywords
- derivative
- greenbrier rhizome
- glabrous greenbrier
- solvent
- weight
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a glabrous greenbrier rhizome A derivative which is characterized by having a structural formula shown as a formula (I):
Description
Technical Field
The invention relates to the technical field of medicines. More particularly, the invention relates to a glabrous greenbrier rhizome A derivative with anti-leukemia activity, a preparation method and application thereof.
Background
Coumarin is a natural product with benzo alpha-pyrone as mother nucleus, and has various biological activities such as antitumor, antioxidant, anti-HIV, anticoagulant, and antimicrobial effects. According to the research trend of modern scholars, the coumarin compound has the advantages of wide source, multiple types, simpler synthesis, small relative molecular mass, high bioavailability and the like, the pharmacological action of the coumarin compound is paid attention and researched by a plurality of scholars, and the coumarin compound has practical value in application and development. The source of plant resources in China is rich, so the development space of the coumarin derivative is large. Two yue huang sandalwood Dalbergia benthami Prain, also named: canna indica, two yue sandalwood, lian, which are born in shrubs and thinning forest,it is distributed in Guangxi, Hainan, Guangdong, etc. The subject group separated a monomeric compound from Dalbergia sanguinea Hance and passed through1HNMR、13CNMR and MS are identified as glabrous greenbrier rhizome A, the structure of the glabrous greenbrier rhizome A is classified as pyranocoumarin, and the content of the compounds in plants is very high and reaches 3.5 percent. The glabrous greenbrier rhizome A (pyranocoumarin) is a macrocyclic conjugated system, has a rigid planar structure and fluorescence, and has the following structure (II):
the primary pharmacological action shows that the glabrous greenbrier rhizome A has obvious scavenging effect on DPPA and ABTS free radicals, the free radicals are related to targets of a plurality of diseases such as leukemia resisting effect, the primary leukemia resisting activity shows that the glabrous greenbrier rhizome A has better activity, and the glabrous greenbrier rhizome A is fully synthesized or semi-synthesized, so that the bottleneck of limited natural sources can be broken through, and the corresponding derivatives are obtained for the structure-activity relationship research. The method uses the glabrous greenbrier rhizome A and the halogenated hydrocarbon to carry out nucleophilic substitution reaction, and carries out structural modification on 4-hydroxyl in the glabrous greenbrier rhizome A to obtain a target product, thereby providing basis and reference for further development and utilization of the pyranocoumarin compound.
Disclosure of Invention
An object of the present invention is to solve at least the above problems and to provide at least the advantages described later.
The invention also aims to provide a glabrous native licorice A derivative with anti-leukemia activity and a preparation method and application thereof, the invention synthesizes the novel glabrous native licorice A derivative by connecting trifluoromethyl benzyl on the 4-position of the glabrous native licorice A, the modified glabrous native licorice A derivative has stronger activity compared with the mother nucleus glabrous licorice A, can be applied to preparing anti-leukemia drugs, can be combined with pharmaceutically acceptable auxiliary materials to prepare injections, tablets, pills, capsules, suspending agents or emulsions, and has the advantages of simple preparation method, easy operation, short reaction time, low cost and less raw material loss.
To achieve these objects and other advantages in accordance with the present invention, there is provided an glabrous greenbrier rhizome A derivative having a structural formula of formula (I):
the invention also provides a preparation method of the glabrous greenbrier rhizome A derivative, which comprises the following steps:
dissolving the glycyrrhiza glabra in a solvent I, adding potassium carbonate into the solvent I, heating the mixture to 80 ℃, and adding p-trifluoromethyl benzyl bromide into the reaction solution in batches at constant temperature;
wherein the molar ratio of the glycyrrhiza glabra to the potassium carbonate to the trifluoromethyl benzyl bromide is 1:0.1: 2-10; the mass ratio of the glycyrrhiza glabra A to the solvent I is 1: 5-10;
step two, controlling the temperature of the reaction liquid to be 60-80 ℃, stopping heating after reacting for 40-60 min, and naturally cooling to room temperature to obtain a reaction product;
and step three, adding water into the reaction product obtained in the step two until the precipitate is completely separated out, filtering to obtain precipitate crystals, extracting for 3 times by using a solvent two pair of precipitate crystals, collecting organic layers obtained by three times of extraction, washing for 3 times by using water to obtain an extract, adding anhydrous sodium sulfate into the extract, drying for 12-18 hours, evaporating the solvent to dryness, and adding anhydrous ethanol for recrystallization to obtain the glycyrrhiza uralensis A derivative.
Preferably, in the preparation method of the glycyrrhiza uralensis A derivative, the first solvent is DMF, and the second solvent is dichloromethane.
The invention also provides application of the glabrous greenbrier rhizome A derivative in preparing antitumor drugs.
Preferably, the application of the glycyrrhiza glabra A derivative is used for preparing anti-leukemia drugs.
Preferably, the application of the glabrous greenbrier rhizome A derivative is that the medicinal preparation comprises an effective amount of the glabrous greenbrier rhizome A derivative and pharmaceutically acceptable auxiliary materials.
Preferably, the application of the glabrous greenbrier rhizome A derivative is that the medicinal preparation is injection, tablet, pill, capsule, suspending agent or emulsion.
Preferably, in the application of the derivative of the glycyrrhiza glabra, the auxiliary materials are one or a combination of more of ethanol, propylene glycol, polyethylene glycol, diethylene glycol, glyceryl triacetate, glycerol, dextrin, povidone, octadecanol, stearic acid, microcrystalline cellulose, starch, lactose, mannitol, sodium bicarbonate, calcium carbonate, low-substituted hydroxypropyl methyl cellulose, magnesium stearate and talcum powder.
The invention at least comprises the following beneficial effects:
1. according to the invention, the 4-position of the glabrous greenbrier rhizome A is connected with the trifluoromethyl benzyl group to synthesize the novel glabrous greenbrier rhizome A derivative, and the modified glabrous greenbrier rhizome A derivative has stronger activity than the parent glabrous greenbrier rhizome A, can be applied to preparation of antitumor drugs, and especially has stronger anti-leukemia activity;
2. the preparation method is simple, easy to operate, short in reaction time and low in cost;
3. in vitro anti-tumor experiments show that the pharmaceutical composition can be combined with pharmaceutically acceptable auxiliary materials to be prepared into various forms of injections, tablets, pills, capsules, suspending agents or emulsions for use.
Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention.
Detailed Description
The present invention is further described in detail below with reference to examples so that those skilled in the art can practice the invention with reference to the description.
It will be understood that terms such as "having," "including," and "comprising," as used herein, do not preclude the presence or addition of one or more other elements or groups thereof.
It is to be noted that the experimental methods described in the following embodiments are all conventional methods unless otherwise specified, and the reagents and materials are commercially available unless otherwise specified.
< example 1>
The invention provides an O-p-trifluoromethyl benzyl earth licorice A derivative, the structural formula of which is shown in the formula (I):
the nuclear magnetic resonance hydrogen spectrum data and the carbon spectrum data of the O-p-trifluoromethyl benzyl soil licorice A derivative are as follows:
1HNMR(CDCl3，600MHz)δ：7.5(d，J＝6Hz，2H，ArH)，7.4(s，2H，ArH)，7.25(s，1H，ArH)，6.9(d，J＝6Hz，2H，ArH)，6.6(t，J＝6Hz，J＝6Hz，2H，ArH)，6.0(s，1H，ArH)，5.7(d，J＝6Hz，1H，ArH)，4.7(d，J＝24Hz，2H，-O-CH2-)，3.87(s，3H，-OCH3)，3.7(d，J＝6Hz，3H，-OCH3)，1.5(s，6H，-CH3)；
13CNMR(CDCl3，150Hz)δ：162.75，159.45，157.27，154.97，152.64，147.48，139.78，132.05，130.81，128.68，128.56，125.16，124.93，124.66，124.63，115.89，115.85，115.15，113.68，112.90，111.27，108.16，105.07，101.24，101.19，77.68，76.79，74.64，63.54，55.32。
< example 2>
The preparation method of the O-p-trifluoromethyl benzyl earth licorice A derivative comprises the following steps:
dissolving glycyrrhiza glabra A in DMF, adding potassium carbonate, heating to 80 ℃, and adding p-trifluoromethyl benzyl bromide to the reaction solution in batches at constant temperature;
wherein, the molar ratio of the glycyrrhiza glabra A to the potassium carbonate to the trifluoromethyl benzyl bromide is 1:0.1: 2; the mass ratio of the glycyrrhiza glabra A to the DMF is 1: 5;
step two, controlling the temperature of the reaction liquid to be 60 ℃, stopping heating after reacting for 40min, and naturally cooling to room temperature to obtain a reaction product;
and step three, adding water into the reaction product obtained in the step two until the precipitate is completely separated out, filtering to obtain precipitate crystals, extracting the precipitate crystals for 3 times by using dichloromethane, collecting organic layers extracted for three times, washing for 3 times by using water to obtain extracts, adding anhydrous sodium sulfate into the extracts, drying for 12 hours, evaporating the solvent to dryness, and adding anhydrous ethanol for recrystallization to obtain the glycyrrhiza uralensis A derivative.
The synthetic route of the O-p-trifluoromethyl benzyl earth licorice A derivative is as follows:
< example 3>
The preparation method of the O-p-trifluoromethyl benzyl earth licorice A derivative comprises the following steps:
dissolving glycyrrhiza glabra A in DMF, adding potassium carbonate, heating to 80 ℃, and adding p-trifluoromethyl benzyl bromide to the reaction solution in batches at constant temperature;
wherein, the molar ratio of the glycyrrhiza glabra A to the potassium carbonate to the trifluoromethyl benzyl bromide is 1:0.1: 10; the mass ratio of the glycyrrhiza glabra A to the DMF is 1: 10;
step two, controlling the temperature of the reaction liquid to be 80 ℃, stopping heating after reacting for 60min, and naturally cooling to room temperature to obtain a reaction product;
and step three, adding water into the reaction product obtained in the step two until the precipitate is completely separated out, filtering to obtain precipitate crystals, extracting the precipitate crystals for 3 times by using dichloromethane, collecting organic layers extracted for three times, washing for 3 times by using water to obtain extracts, adding anhydrous sodium sulfate into the extracts, drying for 18 hours, evaporating the solvent to dryness, and adding anhydrous ethanol for recrystallization to obtain the glycyrrhiza uralensis A derivative.
The synthetic route of the O-p-trifluoromethyl benzyl earth licorice A derivative is as follows:
< example 4>
The preparation method of the O-p-trifluoromethyl benzyl earth licorice A derivative comprises the following steps:
dissolving glycyrrhiza glabra A in DMF, adding potassium carbonate, heating to 80 ℃, and adding p-trifluoromethyl benzyl bromide to the reaction solution in batches at constant temperature;
wherein, the molar ratio of the glycyrrhiza glabra A to the potassium carbonate to the trifluoromethyl benzyl bromide is 1:0.1: 6; the mass ratio of the glycyrrhiza glabra A to the DMF is 1: 8;
step two, controlling the temperature of the reaction liquid to be 70 ℃, stopping heating after reacting for 50min, and naturally cooling to room temperature to obtain a reaction product;
and step three, adding water into the reaction product obtained in the step two until the precipitate is completely separated out, filtering to obtain precipitate crystals, extracting the precipitate crystals for 3 times by using dichloromethane, collecting organic layers extracted for three times, washing for 3 times by using water to obtain extracts, adding anhydrous sodium sulfate into the extracts, drying for 15 hours, evaporating the solvent to dryness, and adding anhydrous ethanol for recrystallization to obtain the glycyrrhiza uralensis A derivative.
The synthetic route of the O-p-trifluoromethyl benzyl earth licorice A derivative is as follows:
< example 5>
A pharmaceutical preparation is prepared by weighing 3 parts by weight of the glabrous greenbrier rhizome A derivative provided by the embodiment 1, 2 parts by weight of propylene glycol and 2 parts by weight of polyethylene glycol, mixing, dissolving in water for injection, filtering to obtain a solution, and filling into an ampoule under aseptic conditions to obtain the injection.
< example 6>
A pharmaceutical preparation is prepared by weighing 2 parts by weight of the glabrous greenbrier rhizome A derivative provided by the embodiment 1, 3 parts by weight of diethylene glycol, 1 part by weight of glyceryl triacetate, 1 part by weight of glycerol, 2 parts by weight of calcium carbonate, 3 parts by weight of low-substituted hydroxypropyl methyl cellulose, 1 part by weight of talcum powder and 8 parts by weight of starch, mixing, uniformly wetting with water, sieving and drying the wetted mixture, adding 1 part by weight of magnesium stearate, and tabletting to obtain the tablet.
< example 7>
A pharmaceutical preparation is prepared by weighing 1 part by weight of the glabrous greenbrier rhizome A derivative provided by the embodiment 1, 1 part by weight of glycerol, 5 parts by weight of dextrin, 1 part by weight of povidone, 1 part by weight of octadecanol, 0.5 part by weight of stearic acid, 0.5 part by weight of microcrystalline cellulose and 0.5 part by weight of lactose, mixing, uniformly wetting with water, sieving and drying the wetted mixture, and rubbing into a spherical shape to obtain the pill.
< example 8>
A pharmaceutical preparation is prepared by weighing 2 parts by weight of the glabrous greenbrier rhizome A derivative provided by the embodiment 1, 2 parts by weight of mannitol, 1.5 parts by weight of sodium bicarbonate, 2 parts by weight of low-substituted hydroxypropyl methylcellulose, 0.5 part by weight of magnesium stearate and 1 part by weight of talcum powder, mixing, sieving, and filling into a gelatin capsule to obtain the capsule.
< example 9>
A pharmaceutical preparation is prepared by weighing 2 parts by weight of the glabrous greenbrier rhizome A derivative provided by the embodiment 1, 5 parts by weight of ethanol, 1 part by weight of polyethylene glycol, 2 parts by weight of calcium carbonate, 1 part by weight of low-substituted hydroxypropyl methylcellulose and 0.5 part by weight of magnesium stearate, and preparing a suspending agent according to a conventional method.
< example 10>
A pharmaceutical preparation is prepared by weighing 2 parts by weight of the glabrous greenbrier rhizome A derivative provided by the embodiment 1, 2 parts by weight of ethanol, 1 part by weight of propylene glycol, 1 part by weight of polyethylene glycol, 2 parts by weight of glycerol, 1 part by weight of dextrin, 3 parts by weight of starch and 0.2 part by weight of lactose, and preparing the mixture into an emulsion according to a conventional method.
< test 1>
Determination of inhibition rate of O-p-trifluoromethyl benzyl earth licorice A on tumor cell line leukemia HL-60:
inoculating cells: preparing single cell suspension by using culture solution (DMEM) containing 10% fetal calf serum, inoculating HL-60 to a 96-well plate by using 3000-15000 cells per hole, wherein the hole volume is 100 mu L, and the cells are inoculated and cultured for 12-24 h in advance;
adding a solution of a compound to be detected: dissolving O-p-trifluoromethyl benzyl soil licorice A and soil licorice A provided by the invention by DMSO respectively to obtain a first sample and a second sample, respectively preparing the first samples with various concentrations and the second samples with various concentrations, respectively adding the first samples with various concentrations and the second samples with various concentrations into a cultured pore plate, wherein the final volume of each pore is 200 mu l, and 3 multiple pores are arranged at each concentration;
③ developing color: after culturing at 37 ℃ for 48 hours, 100. mu.l of the culture supernatant per well was discarded, and 20. mu.l of MTS solution was added to each well; setting 3 blank multiple wells (mixed solution of 20 mul MTS solution and 100 mul culture solution), and continuously incubating 3 control multiple wells (cell suspension) for 2-4 hours to ensure that the light absorption value is measured after the reaction is fully performed;
and fourthly, color comparison: selecting 492nm wavelength, reading the light absorption value of each hole by a multifunctional enzyme labeling instrument (MULTISKAN FC), recording the OD average value result corresponding to each concentration, calculating the cell survival rate of each concentration, drawing a cell growth curve by taking the sample concentration as an abscissa and the cell survival rate as an ordinate, and calculating the IC of the first sample and the second sample by using a two-point method (Reed and Muench method)50A value;
cell survival rate ═ ODSample set-ODBlank group)/(ODControl group-ODBlank group)×100％。
TABLE 1 IC of HL-60 cells50Value of
| IC50(μM) | |
| Sample No | 14.79±1.06 |
| Sample No. 2 | -- |
As can be seen from Table 1, the sample I, namely O-p-trifluoromethyl benzyl soil licorice A provided by the invention has good inhibitory activity on leukemia HL-60, and is far higher than that of the parent soil licorice A.
< test 2>
Toxicity detection experiment for zebra fish
2.1 Experimental materials:
selecting wild AB male zebra fish provided by southern medical university zebra fish experimental center, wherein the fish culture system is a water purification system of Beijing Aisheng company, the temperature of the system is 28.5-29.5 ℃, the salt concentration is 0.03-0.04%, the pH is 7.2-7.6, the illumination is controlled for 14h day and night, and the specific time is 8:30 am-10: 30pro), 10h night;
the zebra fish culture solution is prepared according to the Zebraphis Book standard (0.137moL/L NaCl, 5.4mmoL/L KCl, 0.25mmoL/L Na)2HPO4，0.44mmoL/L KH2PO4，1.3mmoL/L CaCl2，1.0mmoL/L MgSO4，4.2mmoL/L NaHCO3)。
2.2 preparation of the liquid medicine
Dissolving radix Rumicis Japonici A with dimethyl sulfoxide (DMSO) to obtain medicinal liquids with concentration of 2.0mg/mL, 1.5mg/mL, and 1mg/mL, respectively, and storing in a refrigerator at-20 deg.C in dark place;
the O-p-trifluoromethyl benzyl earth licorice A prepared by the invention is dissolved with dimethyl sulfoxide (DMSO) to prepare liquid medicines with the concentration of 2.0mg/mL, 1.5mg/mL and 1mg/mL respectively, and the liquid medicines are placed in a refrigerator for storage at minus 20 ℃ in a dark place.
2.3 methods of embryo handling
Selecting zebrafish embryos which normally develop for 6h (6hpf) under an upright microscope, and randomly transferring the zebrafish embryos into sample wells of 6-well plates, wherein each well contains 20 zebrafish embryos;
100 μ L of each concentration of the liquid medicine and zebra fish culture solution were added to each well so that each well contained a final concentration of 2% DMSO, and a pure hatching solution group (control group) and a hatching solution group containing 2% DMSO were set. Exposing the medicine for 72h, and repeating each experiment for 3 times to reduce experimental errors as much as possible, wherein the embryos are fertilized embryos of the same batch;
zebrafish embryos were placed individually in 6-well plates and incubated with 5 concentration gradients (1%, 2%, 3%, 4%, 5%) in 1% -5% DMSO, 20 embryos per group, and 3 replicates per group. Mainly observing the incidence rate of death or deformity caused by DMSO with different concentrations to zebra fish embryos;
2.4 data processing
Analyzing the death rate and teratogenesis rate of the zebra fish embryos in different drug concentrations by adopting a probability unit method, wherein each series represents the death rate and teratogenesis rate of the drugs after the drugs are exposed for 72 hours; the mortality and the aberration rate among the groups are compared by SPSS 13.0 chi-square test, and the statistical significance is achieved when P is less than 0.05.
2.5 results and discussion
The observation indexes of zebra fish embryos are as follows:
class i indices (lethality indices): eggs are coagulated, have no heartbeat and do not hatch;
class ii indicators (non-lethal indicators revealing a specific mode of action of the test drug): no blood circulation, abnormal development and delayed hatching;
in experiments on the influence of DMSO at various concentrations on zebra fish, 1% and 2% DMSO have little influence on zebra fish embryos. However, when the concentration reaches more than 3%, the development of the embryo to the membrane is greatly influenced, the spinal curvature is severe, and all embryos have no membrane when the concentration is 5% DMSO at 48hpf, and even have a rotting tendency. Since the target product is poorly water soluble, precipitation still occurs in 1% DMSO, the experiment used 2% DMSO to dissolve the target product. 72hpf series were selected to represent the drug zebrafish embryo (72hpf) for statistics of teratogenesis and mortality.
TABLE 2 comparison of teratogenicity and mortality of zebrafish embryos (72hpf) (n ═ 20)
As can be seen from Table 2, the compounds have different degrees of deformity at different concentrations, such as no hatching, egg coagulation, spinal curvature and pericardial enlargement, the sum of the death rate and the teratogenesis rate of the embryo increases with the increase of the concentration of each compound, and shows dose-effect relationship, the embryos of the pure hatching solution group and the hatching solution group with 2% DMSO have normal development, and emerge on time, the glabrous greenbrier rhizome A generally shows stronger toxicity, in the compound 2.0mg/L group, the sum of the death rate and the teratogenesis rate of the zebrafish reaches 100%, the death rate reaches 45%, the embryotoxicity is shown, and the death rate and the teratogenesis rate of the O-p-trifluoromethyl benzyl earth glabrous greenbrier rhizome A to the zebrafish are lower than that of the glabrous greenbrier rhizome A. Compared with the control group, the drug-containing experimental group has statistical significance on the difference of the death rate and the teratocardiology rate (P < 0.01).
The number of apparatuses and the scale of the process described herein are intended to simplify the description of the present invention. Applications, modifications and variations of the present invention will be apparent to those skilled in the art.
While embodiments of the invention have been disclosed above, it is not limited to the applications listed in the description and the embodiments, which are fully applicable in all kinds of fields of application of the invention, and further modifications may readily be effected by those skilled in the art, so that the invention is not limited to the specific details without departing from the general concept defined by the claims and the scope of equivalents.
Claims (7)
1. The glabrous greenbrier rhizome A derivative is characterized by having a structural formula shown as a formula (I):
2. the method for preparing the glycyrrhiza glabra derivative according to claim 1, comprising the steps of:
dissolving the glycyrrhiza glabra in a solvent I, adding potassium carbonate into the solvent I, heating the mixture to 80 ℃, and adding p-trifluoromethyl benzyl bromide into the reaction solution in batches at constant temperature;
wherein the molar ratio of the glycyrrhiza glabra to the potassium carbonate to the trifluoromethyl benzyl bromide is 1:0.1: 2-10; the mass ratio of the glycyrrhiza glabra A to the solvent I is 1: 5-10;
step two, controlling the temperature of the reaction liquid to be 60-80 ℃, stopping heating after reacting for 40-60 min, and naturally cooling to room temperature to obtain a reaction product;
and step three, adding water into the reaction product obtained in the step two until the precipitate is completely separated out, filtering to obtain precipitate crystals, extracting for 3 times by using a solvent two pair of precipitate crystals, collecting organic layers obtained by three times of extraction, washing for 3 times by using water to obtain an extract, adding anhydrous sodium sulfate into the extract, drying for 12-18 hours, evaporating the solvent to dryness, and adding anhydrous ethanol for recrystallization to obtain the glycyrrhiza uralensis A derivative.
3. The method for preparing the glabrous greenbrier rhizome A derivative according to claim 2, wherein the first solvent is DMF and the second solvent is dichloromethane.
4. Use of the derivative of glabrous greenbrier rhizome A according to claim 1 for the preparation of an anti-leukemia drug.
5. The use of a derivative of glabrous greenbrier rhizome according to claim 4, wherein the pharmaceutical preparation comprises an effective amount of glabrous greenbrier rhizome A derivative and a pharmaceutically acceptable excipient.
6. The use of the derivative of glabrous greenbrier rhizome A according to claim 5, wherein the pharmaceutical preparation is an injection, a tablet, a pill, a capsule, a suspension, or an emulsion.
7. The use of the derivative of glabrous greenbrier rhizome A according to claim 6, wherein the auxiliary material is one or a combination of ethanol, propylene glycol, polyethylene glycol, diethylene glycol, glyceryl triacetate, glycerin, dextrin, povidone, stearyl alcohol, stearic acid, microcrystalline cellulose, starch, lactose, mannitol, sodium bicarbonate, calcium carbonate, low-substituted hydroxypropyl methylcellulose, magnesium stearate, and talc.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811168473.7A CN109438461B (en) | 2018-10-08 | 2018-10-08 | Tuliquiritigenin A derivative with anti-leukemia activity and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811168473.7A CN109438461B (en) | 2018-10-08 | 2018-10-08 | Tuliquiritigenin A derivative with anti-leukemia activity and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109438461A CN109438461A (en) | 2019-03-08 |
| CN109438461B true CN109438461B (en) | 2021-04-20 |
Family
ID=65546149
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811168473.7A Active CN109438461B (en) | 2018-10-08 | 2018-10-08 | Tuliquiritigenin A derivative with anti-leukemia activity and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109438461B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111217824B (en) * | 2020-02-25 | 2022-09-23 | 广西大学 | 4-O-arylaminopropyl glycyrrhiza A derivative and preparation and application thereof |
| CN111217825B (en) * | 2020-02-25 | 2022-09-20 | 广西大学 | 4-O-aminopropyl earth licorice A derivative and preparation and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1425667A (en) * | 2001-12-12 | 2003-06-25 | 方宏勋 | New compound with anti-tumor function, its preparing method and use in preparing medicine for curing tumor |
| US20040162337A1 (en) * | 2003-01-30 | 2004-08-19 | Fong Wang Fun | Chemical compounds having therapeutic activities in treating cancer |
| CN1636997A (en) * | 2003-11-13 | 2005-07-13 | 中国人民解放军军事医学科学院毒物药物研究所 | Substituted tricyclocoumarin compound and its prepn and anti-HIV application |
| CN102796112A (en) * | 2011-05-25 | 2012-11-28 | 复旦大学 | Prenylflavonoid compound and application thereof in preparation of pancrelipase inhibitor |
| CN105287511A (en) * | 2015-11-25 | 2016-02-03 | 广西中医药大学 | Application of 3-phenylcoumarin robustic acid |
-
2018
- 2018-10-08 CN CN201811168473.7A patent/CN109438461B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1425667A (en) * | 2001-12-12 | 2003-06-25 | 方宏勋 | New compound with anti-tumor function, its preparing method and use in preparing medicine for curing tumor |
| US20040162337A1 (en) * | 2003-01-30 | 2004-08-19 | Fong Wang Fun | Chemical compounds having therapeutic activities in treating cancer |
| CN1636997A (en) * | 2003-11-13 | 2005-07-13 | 中国人民解放军军事医学科学院毒物药物研究所 | Substituted tricyclocoumarin compound and its prepn and anti-HIV application |
| CN102796112A (en) * | 2011-05-25 | 2012-11-28 | 复旦大学 | Prenylflavonoid compound and application thereof in preparation of pancrelipase inhibitor |
| CN105287511A (en) * | 2015-11-25 | 2016-02-03 | 广西中医药大学 | Application of 3-phenylcoumarin robustic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109438461A (en) | 2019-03-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101255119B (en) | Novel tetrahydro curcumin derivatives and salt | |
| CN109438461B (en) | Tuliquiritigenin A derivative with anti-leukemia activity and preparation method and application thereof | |
| CN106632572B (en) | A kind of Astragaloside IV derivative and its preparation method and application | |
| CN111494390B (en) | New application of betulin derivative in preparing medicine for repairing nerve injury | |
| EP3339285A1 (en) | A compound isolated from isodon forrestii var. forrestii and preparation method and applications thereof | |
| CN108350023A (en) | A kind of compound and its preparation method and application with antitumaous effect | |
| CN109438462B (en) | O-p-nitrobenzoyl earthy licorice A with antineoplastic activity and preparation method and application thereof | |
| CN109232601A (en) | With active native Radix Glycyrrhizae A derivative of anti-cervical cancer and its preparation method and application | |
| CN109232600B (en) | O-p-methylbenzyl earth licorice A with antitumor activity, preparation method, pharmaceutical preparation and application | |
| BRPI0806461B1 (en) | maleic acid monomer, and pharmaceutical composition for the prevention or treatment of viral infections | |
| CN109438463B (en) | O- (4-bromo-2-fluorobenzoyl) glabra with anti-tumor activity, and preparation method and application thereof | |
| CN110590779B (en) | 3, 10 di-p-chlorophenyl 6, 12 diazatetracubane compound, and synthetic method, application and pharmaceutical composition thereof | |
| CN111217825B (en) | 4-O-aminopropyl earth licorice A derivative and preparation and application thereof | |
| US6451846B1 (en) | Isocoumarin derivatives inhibiting angiogenesis | |
| CN109232599B (en) | O-p-trifluoromethyl benzoyl soil licorice A with antitumor activity and its prepn and use | |
| CN104693121A (en) | Pyrazol compounds with anti-senile dementia activity as well as preparation method and application of pyrazol compounds | |
| CN108310125B (en) | Application of Qianliexin in antithrombotic drugs | |
| CN111467331B (en) | Application of 1-indanone in preparation of medicine for treating or preventing autosomal dominant hereditary polycystic kidney disease | |
| CN101857591A (en) | Hydrochloric acid tiagabine crystal formations and preparation method thereof | |
| CN111499605A (en) | Isopentene chromone compound and preparation method and application thereof | |
| CN113995762B (en) | Application of phellodendron ketone in preparing medicine for treating autosomal dominant hereditary polycystic kidney disease | |
| KR101629558B1 (en) | A Naphthochalcone and use of the same as anticancer drug | |
| CN115322204B (en) | Preparation method and application of radix glycyrrhizae glabra A and derivatives thereof | |
| CN1961876A (en) | Use of phthalimide derivative in preparation of medicament for resisting angiogenesis | |
| CN103265537B (en) | Antitumor compounds, preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |