CN103102360B - Alanine copper complex as well as preparation method and application thereof - Google Patents
Alanine copper complex as well as preparation method and application thereof Download PDFInfo
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Abstract
The invention provides an alanine copper complex as well as a preparation method and an application thereof. The alanine copper complex has coordination of lactamine and copper ions and can also contain other organic micro-molecular ligands. The preparation method of the alanine copper complex comprises the following steps of: putting lactamine, a cupric salt, alkali and other organic micro-molecular ligands into a solvent, and stirring for reaction to obtain the alanine copper complex. The alanine copper complex is easily available in synthetic raw material and low in cost, and the product is separated out in the form of crystal and is high in purity and yield; the alanine copper complex can stably exist in a natural state and has high water solubility and fat solubility; and moreover, the alanine copper complex has a good function of inhibiting a variety of cancer cells such as cells of lung cancer, stomach cancer, liver cancer, colonic gland, leukemia, nasopharyngeal darcinoma and the like, and is wide in action spectrum and application range.
Description
Technical field
The present invention relates to class L-Ala copper complex and preparation method thereof, and the application of such title complex in the medicine preparing prevention and therapy cancer and tumor disease.
Background technology
Amino acid is the foundation stone forming life entity albumen, and, all the other materials of 80% are albumen, are specifically amino acid in cell than water.Nitrite, for can react with nitrite, is become nitrogen G&W by an amino acid whose important chemical property.Especially the reaction of a-amino acid and nitrite is very fast, and can transfer completely quantitative for nitrite to nitrogen, reacts as follows:
R-C(NH
2)HCOOH+HNO
2→R-C(OH)HCOOH+N
2+H
2O
And nitrite is one of important group causing cancer to occur.
Copper is the indispensable important trace element of human body, and relevant research shows, copper lacks not only makes cancer of the stomach, nasopharyngeal carcinoma sickness rate rise, but also relevant with onset of liver cancer rate.As far back as 1912, the patient suffering from facial cancer just treated with the mixture that a kind of muriate by copper and LECITHIN form in Germany, and the successful explanation copper compound of this treatment has anti-cancer function.The research work carried out in Liverpool University for 1913 illustrates: by subcutaneously can softening with intravenous injection mantoquita and electrocuprol or eliminating the cancer knurl be implanted in mouse body.Nineteen thirty, show in the research work of France: shift by injection electrocuprol and eliminate tumor tissues.The research work carried out in the U.S. recently shows: by take appropriate various copper complex treat solid tumour can the growth of obvious Tumor suppression and transfer, improve the probability of surviving.
But, up to now, still amino acid copper complex is not carried out the prevention and therapy of cancer and tumour at present as clinical medicine.Amino acid is coordinated with copper and both can improve the fat-soluble of metal copper ion, can improve again amino acid whose water-soluble, and the anti-cancer function of Mutiple Targets can be exercised simultaneously.
Summary of the invention
The object of this invention is to provide L-Ala copper complex, L-Ala and mantoquita carry out the title complex that coordinates specifically, and preparation method thereof and application in the medicine preparing prevention and therapy cancer and tumor disease.
For achieving the above object, the present invention adopts following technical scheme:
Amino acid copper complex provided by the present invention, by amino acid and cupric ion coordination, and auxiliary other organic micromolecule ligand composition.
Wherein, other organic micromolecule ligand described is selected from 1,10-phenanthroline and derivative, counter ion and/or water molecules.
Its molecular structural formula is:
[(n-Phen)Cu(Ala)(OAla)Cu(n-phen)·XY]
m，
Wherein: Ala is L-Ala; N-(Phen) is 1,10-phenanthroline, or 1,10-derivative of phenanthroline of unit or multidigit replacement; Cu is divalence or univalent copper ion; M be 1 or be greater than 1 integer; X is counter ion, and Y is the filling water molecules optionally existed.
Described unit or multidigit replace 1, 10-phenanthroline substitutive derivative is that 2-replaces, 2, 3-replaces, 2, 4-replaces, 2, 5-replaces, 2, 6-replaces, 2, 7-replaces, 2, 8-replaces, 2, 9-replaces, 3-replaces, 3, 4-replaces, 3, 5-replaces, 3, 6-replaces, 3, 7-replaces, 3, 8-replaces, 3, 9-replaces, 4-replaces, 4, 5-replaces, 4, 6-replaces, 4, 7-replaces, 4, 8-replaces, 4, 9-replaces, 5-replaces, 5, 6-replaces, 5, 7-replaces, 5, 8-replaces, 5, 9-replaces, 6-replaces, 6, 7-replaces, 6, 8-replaces, 6, 9-replaces, 7-replaces, 7, 8-replaces, 7, 9-replaces, 8-replaces, 8, 9-replaces, 9-replaces, and 1 of other 3 or multidigit, 10-phenanthroline substitutive derivative, described substituting group is alkyl, nitro, amino or halogen etc.Described alkyl preferable methyl, the preferred chlorine of described halogen.
Described counter ion refer to the negative ions such as nitrate radical, sulfate radical, acetate moiety or halide-ions.
In molecular structural formula, the end group O atomic bond of an end group C atom of the Ala of (OAla) and and Cu Atomic coordinate and, formed (-Cu-Ala-O-Cu-Ala-O-)
mone dimension key bridge, m be 1 or be greater than 1 integer, can convergence infinite.[(n-Phen) Cu (Ala) (OAla) Cu (n-phen)]
mfor basic structural unit, periodically repeat to form macroscopical crystal.
The present invention also provides the preparation method of described amino acid whose copper complex, by mantoquita and L-Ala, alkali and 1,10-phenanthroline and derivative thereof constantly stir in a solvent, filter after stoichiometric number hour, leave standstill, or with leaving standstill after the mixed solvent diffusion of multiple organic solvent or leaving standstill with after ether diffusion, after several days, obtain described title complex.
Wherein, described mantoquita is inorganic mantoquita or organic copper salt and their hydrate, or their mixture.Described inorganic mantoquita is cupric nitrate, cupric chloride, copper sulfate and its hydrate etc. such as, and described organic copper salt is venus crystals and its hydrate etc. such as.
Wherein, described alkali is selected from sodium hydroxide, potassium hydroxide, hydrated barta or ammoniacal liquor.
Described solvent is the mixed solvent of single organic solvent or multiple organic solvent or the mixed solvent of single inorganic solvent or organic solvent and inorganic solvent, described organic solvent such as N, dinethylformamide (DMF), N, N-N,N-DIMETHYLACETAMIDE (DMA), methyl-sulphoxide (DMSO), methyl alcohol, ethanol, ethylene glycol, propylene glycol, glycerol, acetone, acetonitrile or methyl ethyl diketone, described inorganic solvent such as water.
The mixed solvent of described multiple organic solvent is as the mixed solvent of the mixed solvent of methyl alcohol and acetonitrile, methyl alcohol and acetone, acetonitrile and the mixed solvent of acetone or the mixed solvent etc. of methylene dichloride and acetonitrile.
The temperature of described reaction can be room temperature, or is warming up to 40-60 degree.
The cell experiment of title complex of the present invention entrusts China Medical institute carry out and provide Activity Results; confirm by experiment; described amino acid copper complex has good growth-inhibiting effect for the cell of the cancers such as leukemia, cancer of the stomach, liver cancer, nasopharyngeal carcinoma, lung cancer and adenocarcinoma of colon; can be widely used in the medicine preparing these cancers of prevention and therapy, the application of this aspect also belongs to protection scope of the present invention.
L-Ala copper complex of the present invention, its synthesis material is easy to get, and cost is low, and product is separated out with crystalline form, and purity is large, and productive rate is high; And this title complex in its natural state can stable existence, and have good water-soluble and fat-soluble; In addition, title complex of the present invention all presents excellent restraining effect for kinds cancer cells such as leukemia, cancer of the stomach, liver cancer, nasopharyngeal carcinoma, lung cancer and adenocarcinoma of colon leukemia, cancer of the stomach, liver cancer, nasopharyngeal carcinoma, lung cancer and adenocarcinoma of colon, action spectrum is wide, has wide range of applications.
Accompanying drawing explanation
Figure 1A is the infrared spectrogram of title complex Z1 of the present invention.
Figure 1B is the X-diffraction single crystal structure figure of title complex Z1 of the present invention.
Fig. 1 C is the molecular structure of title complex Z1 of the present invention.
Fig. 1 D is the structure cell accumulation graph of title complex Z1 of the present invention.
Fig. 2 A is the infrared spectrogram of title complex Z2 of the present invention.
Fig. 2 B is the X-diffraction single crystal structure figure of title complex Z2 of the present invention.
Fig. 3 A is the infrared spectrogram of title complex Z3 of the present invention.
Fig. 3 B is the X-diffraction single crystal structure figure of title complex Z3 of the present invention.
Fig. 4 A is the infrared spectrogram of title complex Z4 of the present invention.
Fig. 4 B is the X-diffraction single crystal structure figure of title complex Z4 of the present invention.
Embodiment
Below in conjunction with embodiment, the invention will be further described, it should be understood that these embodiments only for the object of illustration, never limit the scope of the invention.
Embodiment 1
The preparation of title complex Z1
By 1mmol cupric nitrate, 1mmol L-Ala and 1mmol sodium hydroxide successively join in 30ml DMF solvent, are warming up to 60 DEG C, stir 5 hours; Then add 1mmol 1,10-phenanthroline, continue stirring 5 hours; Filtration, gets clear liquid and ether spreads, and obtains mazarine needle-like crystal Z1 after a couple of days.
Z1 compound molecule formula is: [(1,10-Phen) Cu (OAla) (Ala) Cu (1,10-phen) NO
3]
m, wherein: Ala is L-Ala, and the end group O atomic bond of an end group C atom of Ala in (OAla) and and Cu Atomic coordinate and, formed (-Cu-Ala-O-Cu-Ala-O-)
mone dimension key bridge, m convergence is infinite.[(1,10-Phen) Cu (OAla) (Ala) Cu (1,10-phen) NO
3]
nperiodically repeat to form macroscopical crystal as crystalline structure primitive, have the NO coexisted in lattice simultaneously
3 -ion is as counter ion (referring to accompanying drawing 1B).Ultimate analysis (%): calculated value (experimental value): C 43.70 (43.66); H 3.88 (3.80); N 13.60 (13.46); 15.54 (15.32).Its infrared spectra and X-diffraction single crystal structure figure are shown in shown in accompanying drawing 1A, 1B respectively, and molecular structure and structure cell accumulation graph are shown in shown in accompanying drawing 1C, 1D respectively.
The cell experiment of title complex Z1
Select the attached tumor cells of logarithmic phase: A-549 (lung cancer), Bel-7402 (liver cancer), HCT (adenocarcinoma of colon), HL-60 (leukemia), BGC-823 (cancer of the stomach), KB (nasopharyngeal carcinoma) are with after trysinization, the cell suspension of 5000/mL is made into the RPM11640 nutrient solution of 10% calf serum, be seeded in 96 well culture plates, 100 μ L are inoculated in every hole, 37 DEG C, 5%CO
2cultivate 24h.
Experimental group: add embodiment 1 gained sample solution 10 μ L (namely use physiological saline solution embodiment 1 gained complex crystal Z1, concentration is 5 μ g/mL), every hole final volume is 200 μ L, supplies with RPMI-1640.37 DEG C, 5%CO
2cultivate 3d.
Supernatant liquor is abandoned after cultivating 3d, every hole adds the serum-free medium of the freshly prepared 0.5mg/mL MTT (tetrazolium bromide) of 100 μ L, 37 DEG C are continued to cultivate 4h, carefully abandon supernatant, and add 200 μ L DMSO dissolving MTT formazon precipitations, with the mixing of miniature ultrasonic vibrator, microplate reader measures the optical density value at wavelength 544nm place.According to following formulae discovery growth of tumour cell inhibiting rate:
Growth of tumour cell inhibiting rate (%)=(OD
contrast-OD
experiment)/(OD
contrast-OD
blank) × 100%
Result shows, embodiment 1 gained title complex Z1 all has good growth-inhibiting effect to kinds of tumor cells, is respectively:
Be 80.95% to A-549 (lung cancer) inhibitory rate of cell growth,
Be 80.34% to Bel-7402 (liver cancer) inhibitory rate of cell growth,
Be 80.60% to HCT (adenocarcinoma of colon) inhibitory rate of cell growth,
Be 80.12% to HL-60 (leukemia) inhibitory rate of cell growth;
Be 80.61% to BGC-823 (cancer of the stomach) inhibitory rate of cell growth;
Be 80.80% to KB (nasopharyngeal carcinoma) inhibitory rate of cell growth;
Conclusion: this shows, title complex Z1 of the present invention can for the preparation of the medicine of prevention and therapy cancer.
Embodiment 2
The preparation of title complex Z2
By 1mmol cupric nitrate, 1mmol L-Ala and 1mmol sodium hydroxide successively join in 30ml methanol solvate, are warming up to 60 DEG C, stir 5 hours; Then add 1mmol1,10-phenanthroline, continue stirring 5 hours; Filter, get clear liquid and ether and spread and within one week, obtain blue needle-like crystal Z2.
The title complex Z1 of title complex Z2 and embodiment 1 is allotrope, and Z2 compound molecule formula is:
[(1，10-Phen)Cu(OAla)(Ala)Cu(1，10-phen)·NO
3]
m。
Wherein: Ala is L-Ala, and the end group O atomic bond of an end group C atom of Ala in (OAla) and and Cu Atomic coordinate and, formed (-Cu-Ala-O-Cu-Ala-O-)
mone dimension key bridge, m convergence is infinite.[(1,10-Phen) Cu (OAla) (Ala) Cu (1,10-phen) NO
3]
mperiodically repeat to form macroscopical crystal as crystalline structure primitive, have the NO coexisted in lattice simultaneously
3 -ion is as counter ion.Ultimate analysis (%): calculated value (experimental value): C 43.70 (43.60); H 3.88 (3.82); N 13.60 (13.45); 15.54 (15.30).Its infrared spectra and X-diffraction single crystal structure figure are shown in accompanying drawing 2A, 2B respectively.
The cell experiment of title complex Z2
Select the attached tumor cells of logarithmic phase: A-549 (lung cancer), Bel-7402 (liver cancer), HCT (adenocarcinoma of colon), HL-60 (leukemia), BGC-823 (cancer of the stomach), KB (nasopharyngeal carcinoma) are with after trysinization, the cell suspension of 5000/mL is made into the RPM11640 nutrient solution of 10% calf serum, be seeded in 96 well culture plates, 100 μ L are inoculated in every hole, 37 DEG C, 5%CO
2cultivate 24h.
Experimental group: add embodiment 2 gained sample solution 10 μ L (namely use physiological saline solution embodiment 2 gained complex crystal Z2, concentration is 5 μ g/mL), every hole final volume is 200 μ L, supplies with RPMI-1640.37 DEG C, 5%CO
2cultivate 3d.
Supernatant liquor is abandoned after cultivating 3d, every hole adds the serum-free medium of the freshly prepared 0.5mg/mL MTT (tetrazolium bromide) of 100 μ L, 37 DEG C are continued to cultivate 4h, carefully abandon supernatant, and add 200 μ L DMSO dissolving MTT formazon precipitations, with the mixing of miniature ultrasonic vibrator, microplate reader measures the optical density value at wavelength 544nm place.According to following formulae discovery growth of tumour cell inhibiting rate:
Growth of tumour cell inhibiting rate (%)=(OD
contrast-OD
experiment)/(OD
contrast-OD
blank) × 100%
Result shows, embodiment 2 gained title complex Z2 all has good growth-inhibiting effect to kinds of tumor cells, is respectively:
Be 80.35% to A-549 (lung cancer) inhibitory rate of cell growth,
Be 80.44% to Bel-7402 (liver cancer) inhibitory rate of cell growth,
Be 80.30% to HCT (adenocarcinoma of colon) inhibitory rate of cell growth,
Be 80.86% to HL-60 (leukemia) inhibitory rate of cell growth;
2 pairs of BGC-823 (cancer of the stomach) inhibitory rate of cell growth are 80.93%;
Be 80.79%. to KB (nasopharyngeal carcinoma) inhibitory rate of cell growth
Conclusion: this illustrates, title complex Z2 of the present invention can for the preparation of the medicine of prevention and therapy cancer.
Embodiment 3
The preparation of title complex Z3
By 1mmol cupric chloride, 1mmol L-Ala and 1mmol sodium hydroxide successively join 30ml (V ethanol: V water=4: 1) in solvent, are warming up to 60 DEG C, stirs 5 hours; Then add 1mmol1,10-phenanthroline, continue stirring 5 hours; Filter, get clear liquid and ether and spread and within one week, obtain blue rhabdolith Z3.
Z3 compound molecule formula is: [(1,10-Phen) Cu (OAla) (Ala) Cu (1,10-phen) ClH
2o]
m, wherein: Ala is L-Ala, and the end group O atomic bond of an end group C atom of Ala in (OAla) and and Cu Atomic coordinate and, formed (-Cu-Ala-O-Cu-Ala-O-)
mone dimension key bridge, m convergence is infinite.[(1,10-Phen) Cu (OAla) (Ala) Cu (1,10-phen) ClH
2o]
mperiodically repeat to form macroscopical crystal as crystalline structure primitive, have the Cl-ion coexisted as counter ion in lattice simultaneously.Ultimate analysis (%): calculated value (experimental value): C 44.85 (44.66); H 3.99 (3.90); N 10.47 (10.46); Cu 15.95 (15.92); Cl8.85 (8.89).Its infrared spectra and X-diffraction single crystal structure figure are shown in accompanying drawing 3A, 3B respectively.
The cell experiment of title complex Z3
Select the attached tumor cells of logarithmic phase: A-549 (lung cancer), Bel-7402 (liver cancer), HCT (adenocarcinoma of colon), HL-60 (leukemia), BGC-823 (cancer of the stomach), KB (nasopharyngeal carcinoma) are with after trysinization, the cell suspension of 5000/mL is made into the RPM11640 nutrient solution of 10% calf serum, be seeded in 96 well culture plates, 100 μ L are inoculated in every hole, 37 DEG C, 5%CO
2cultivate 24h.
Experimental group: add embodiment 3 gained sample solution 10 μ L (namely use physiological saline solution embodiment 2 gained complex crystal Z2, concentration is 5 μ g/mL), every hole final volume is 200 μ L, supplies with RPMI-1640.37 DEG C, 5%CO
2cultivate 3d.
Supernatant liquor is abandoned after cultivating 3d, every hole adds the serum-free medium of the freshly prepared 0.5mg/mL MTT (tetrazolium bromide) of 100 μ L, 37 DEG C are continued to cultivate 4h, carefully abandon supernatant, and add 200 μ L DMSO dissolving MTT formazon precipitations, with the mixing of miniature ultrasonic vibrator, microplate reader measures the optical density value at wavelength 544nm place.According to following formulae discovery growth of tumour cell inhibiting rate:
Growth of tumour cell inhibiting rate (%)=(OD
contrast-OD
experiment)/(OD
contrast-OD
blank) × 100%
Result shows, embodiment 3 gained title complex Z3 all has good growth-inhibiting effect to kinds of tumor cells, is respectively:
Be 80.56% to A-549 (lung cancer) inhibitory rate of cell growth,
Be 80.66% to Bel-7402 (liver cancer) inhibitory rate of cell growth,
Be 80.35% to HCT (adenocarcinoma of colon) inhibitory rate of cell growth,
Be 80.89% to HL-60 (leukemia) inhibitory rate of cell growth;
2 pairs of BGC-823 (cancer of the stomach) inhibitory rate of cell growth are 80.83%;
Be 80.89%. to KB (nasopharyngeal carcinoma) inhibitory rate of cell growth
Conclusion: this illustrates, title complex Z3 of the present invention can for the preparation of the medicine of prevention and therapy cancer.
Embodiment 4
The preparation of title complex Z4
By 1mmol cupric nitrate, 1mmol L-Ala and 1mmol sodium hydroxide successively join 30ml (V ethanol: V water=4: 1) in solvent, are warming up to 60 DEG C, stirs 5 hours; Then add 1mmol 2,9 dimethyl-1,10-phenanthrolines, continue stirring 5 hours; Filter, get clear liquid and ether and spread and obtain a sky blue needle-like crystal in.
Z4 compound molecule formula is:
{ [2,9-CH
3-(1,10-Phen)] Cu (OAla) (Ala) Cu [2,9-CH
3-(1,10-Phen)] NO
3h
2o}
m, wherein: Ala is L-Ala, and the end group O atomic bond of an end group C atom of Ala in (OAla) and and Cu Atomic coordinate and, formed (-Cu-Ala-O-Cu-Ala-O-)
mone dimension key bridge, m convergence is infinite.{ [2,9-CH
3-(1,10-Phen)] Cu (OAla) (Ala) Cu [2,9-CH
3-(1,10-Phen)] NO
3h
2o}
mperiodically repeat to form macroscopical crystal as crystalline structure primitive, have the NO coexisted in lattice simultaneously
3 -ion as counter ion, and fills water molecules.Ultimate analysis (%): calculated value (experimental value): C 44.75 (44.76); H 4.39 (4.30); N 12.29 (12.26); Cu14.04 (14.02).Its infrared spectra and X-diffraction single crystal structure figure are shown in accompanying drawing 4A, 4B respectively.
The cell experiment of title complex Z4
Select the attached tumor cells of logarithmic phase: A-549 (lung cancer), Bel-7402 (liver cancer), HCT (adenocarcinoma of colon), HL-60 (leukemia), BGC-823 (cancer of the stomach), KB (nasopharyngeal carcinoma) are with after trysinization, the cell suspension of 5000/mL is made into the RPM11640 nutrient solution of 10% calf serum, be seeded in 96 well culture plates, 100 μ L are inoculated in every hole, 37 DEG C, 5%CO
2cultivate 24h.
Experimental group: add embodiment 4 gained sample solution 10 μ L (namely use physiological saline solution embodiment 2 gained complex crystal Z2, concentration is 5 μ g/mL), every hole final volume is 200 μ L, supplies with RPMI-1640.37 DEG C, 5%CO
2cultivate 3d.
Supernatant liquor is abandoned after cultivating 3d, every hole adds the serum-free medium of the freshly prepared 0.5mg/mL MTT (tetrazolium bromide) of 100 μ L, 37 DEG C are continued to cultivate 4h, carefully abandon supernatant, and add 200 μ L DMSO dissolving MTT formazon precipitations, with the mixing of miniature ultrasonic vibrator, microplate reader measures the optical density value at wavelength 544nm place.According to following formulae discovery growth of tumour cell inhibiting rate:
Growth of tumour cell inhibiting rate (%)=(OD
contrast-OD
experiment)/(OD
contrast-OD
blank) × 100%
Result shows, embodiment 4 gained title complex Z4 all has good growth-inhibiting effect to kinds of tumor cells, is respectively:
Be 80.26% to A-549 (lung cancer) inhibitory rate of cell growth,
Be 80.76% to Bel-7402 (liver cancer) inhibitory rate of cell growth,
Be 80.25% to HCT (adenocarcinoma of colon) inhibitory rate of cell growth,
Be 80.79% to HL-60 (leukemia) inhibitory rate of cell growth;
2 pairs of BGC-823 (cancer of the stomach) inhibitory rate of cell growth are 80.88%;
Be 80.69%. to KB (nasopharyngeal carcinoma) inhibitory rate of cell growth
Conclusion: this illustrates, title complex Z4 of the present invention can for the preparation of the medicine of prevention and therapy cancer.
The foregoing is only preferred embodiment of the present invention, is only illustrative for the purpose of the present invention, and nonrestrictive.Those skilled in the art is understood, and can carry out many changes in the spirit and scope that the claims in the present invention limit to it, amendment, even equivalence, but all will fall within the scope of protection of the present invention.
Claims (11)
1. a seed amino acid copper complex, by amino acid and cupric ion coordination, and auxiliary other organic micromolecule ligand composition, wherein, other organic micromolecule ligand described is selected from 1,10-phenanthroline and derivative, counter ion and/or water molecules, and the molecular structural formula of described title complex is:
[(n-Phen)Cu(Ala)(OAla)Cu(n-phen)·XY]
m，
Wherein: Ala is L-Ala; N-(Phen) is 1,10-phenanthroline, or 1,10-derivative of phenanthroline of unit or multidigit replacement; Cu is divalence or univalent copper ion; M be 1 or be greater than 1 integer; X is counter ion, and Y is the filling water molecules optionally existed;
In molecular structural formula, the end group O atomic bond of an end group C atom of the Ala of (OAla) and and Cu Atomic coordinate and, formed (-Cu-Ala-O-Cu-Ala-O-)
mone dimension key bridge, m be 1 or be greater than 1 integer, can convergence infinite; [(n-Phen) Cu (Ala) (OAla) Cu (n-phen)]
mfor basic structural unit, periodically repeat to form macroscopical crystal.
2. title complex according to claim 1, described unit or multidigit replace 1, 10-phenanthroline substitutive derivative is that 2-replaces, 2, 3-replaces, 2, 4-replaces, 2, 5-replaces, 2, 6-replaces, 2, 7-replaces, 2, 8-replaces, 2, 9-replaces, 3-replaces, 3, 4-replaces, 3, 5-replaces, 3, 6-replaces, 3, 7-replaces, 3, 8-replaces, 3, 9-replaces, 4-replaces, 4, 5-replaces, 4, 6-replaces, 4, 7-replaces, 4, 8-replaces, 4, 9-replaces, 5-replaces, 5, 6-replaces, 5, 7-replaces, 5, 8-replaces, 5, 9-replaces, 6-replaces, 6, 7-replaces, 6, 8-replaces, 6, 9-replaces, 7-replaces, 7, 8-replaces, 7, 9-replaces, 8-replaces, 8, 9-replaces, 9-replaces, and 1 of other 3 or multidigit, 10-phenanthroline substitutive derivative, described substituting group is alkyl, nitro, amino or halogen.
3. title complex according to claim 2, described alkyl is methyl, and described halogen is chlorine.
4. title complex according to claim 1, described counter ion refer to nitrate radical, sulfate radical, acetate moiety or halide-ions.
5. prepare the method for the arbitrary described title complex of claim 1-4 for one kind, by mantoquita and L-Ala, alkali and 1,10-phenanthroline and derivative thereof constantly stir in a solvent, filter after stoichiometric number hour, leave standstill, or with leaving standstill after the mixed solvent diffusion of multiple organic solvent or leaving standstill with after ether diffusion, after several days, obtain described title complex.
6. method according to claim 5, wherein, described mantoquita is inorganic mantoquita or organic copper salt and their hydrate, or their mixture;
7. method according to claim 6, wherein, described inorganic mantoquita is cupric nitrate, cupric chloride, copper sulfate and its hydrate, and described organic copper salt is venus crystals and its hydrate.
8. method according to claim 5, wherein, described alkali is selected from sodium hydroxide, potassium hydroxide, hydrated barta or ammoniacal liquor.
9. method according to claim 5, described solvent is the mixed solvent of single organic solvent or multiple organic solvent or the mixed solvent of single inorganic solvent or organic solvent and inorganic solvent;
10. method according to claim 9, described organic solvent is N, dinethylformamide, N,N-dimethylacetamide, methyl-sulphoxide, methyl alcohol, ethanol, ethylene glycol, propylene glycol, glycerol, acetone, acetonitrile or methyl ethyl diketone, described inorganic solvent is water; The mixed solvent of described multiple organic solvent is the mixed solvent of the mixed solvent of methyl alcohol and acetonitrile, methyl alcohol and acetone, acetonitrile and the mixed solvent of acetone or the mixed solvent of methylene dichloride and acetonitrile.
The arbitrary described title complex of 11. claim 1-4 is preparing the application in prevention and therapy cancer and tumour medicine.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5576326A (en) * | 1989-12-20 | 1996-11-19 | Universidad Nacional Autonoma De Mexico (Unam) | Copper amino acidate diimine nitrate compounds and their methyl derivatives and a process for preparing them |
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2011
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5576326A (en) * | 1989-12-20 | 1996-11-19 | Universidad Nacional Autonoma De Mexico (Unam) | Copper amino acidate diimine nitrate compounds and their methyl derivatives and a process for preparing them |
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| Title |
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| Electrical Conduction in Some Ternary Metallo-Organic Solid Complexes of Biological Importance and Compensation Effect;Mallik, Biswanath;《Bull. Chem. Soc. Jpn.》;19891231;第62卷(第12期);4086-4088 * |
| 张志军 等.两种氨基酸-邻菲啰啉-铜(Ⅱ)三元配合物与DNA作用的研究.《华中师范大学学报(自然科学版)》.2008,第42卷(第3期),409-414. * |
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