CN101434525A - 4-(4-hydroxy3-methoxybenzene methyl) curcumin and use thereof in preparing anti-tumor medicament - Google Patents
4-(4-hydroxy3-methoxybenzene methyl) curcumin and use thereof in preparing anti-tumor medicament Download PDFInfo
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- CN101434525A CN101434525A CN 200810071179 CN200810071179A CN101434525A CN 101434525 A CN101434525 A CN 101434525A CN 200810071179 CN200810071179 CN 200810071179 CN 200810071179 A CN200810071179 A CN 200810071179A CN 101434525 A CN101434525 A CN 101434525A
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- curcumine
- methoxybenzene
- methoxybenzene methyl
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- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 title claims abstract description 51
- 239000003814 drug Substances 0.000 title claims abstract description 8
- 235000012754 curcumin Nutrition 0.000 title abstract description 4
- 229940109262 curcumin Drugs 0.000 title abstract description 4
- 239000004148 curcumin Substances 0.000 title abstract description 4
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 title abstract description 4
- 230000000259 anti-tumor effect Effects 0.000 title description 7
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 claims abstract description 9
- 235000012141 vanillin Nutrition 0.000 claims abstract description 9
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- 206010009944 Colon cancer Diseases 0.000 claims abstract description 4
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 3
- 206010060862 Prostate cancer Diseases 0.000 claims abstract description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims abstract description 3
- 208000032839 leukemia Diseases 0.000 claims abstract description 3
- 201000000849 skin cancer Diseases 0.000 claims abstract description 3
- 201000011510 cancer Diseases 0.000 claims abstract 2
- 239000002246 antineoplastic agent Substances 0.000 claims description 6
- 229940041181 antineoplastic drug Drugs 0.000 claims description 6
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 208000014018 liver neoplasm Diseases 0.000 claims description 3
- 201000000498 stomach carcinoma Diseases 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 238000005882 aldol condensation reaction Methods 0.000 claims description 2
- 201000010989 colorectal carcinoma Diseases 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 201000008261 skin carcinoma Diseases 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 230000000118 anti-neoplastic effect Effects 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 206010017758 gastric cancer Diseases 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- IFGDRUTWCITGHG-UHFFFAOYSA-N 3-[(4-hydroxy-3-methoxyphenyl)methyl]pentane-2,4-dione Chemical compound COC1=CC(CC(C(C)=O)C(C)=O)=CC=C1O IFGDRUTWCITGHG-UHFFFAOYSA-N 0.000 abstract 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 abstract 2
- 201000009030 Carcinoma Diseases 0.000 abstract 1
- 208000000453 Skin Neoplasms Diseases 0.000 abstract 1
- 230000002440 hepatic effect Effects 0.000 abstract 1
- 201000011549 stomach cancer Diseases 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 230000000452 restraining effect Effects 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 4
- JKWMSGQKBLHBQQ-UHFFFAOYSA-N diboron trioxide Chemical compound O=BOB=O JKWMSGQKBLHBQQ-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000003945 NF-kappa B Human genes 0.000 description 2
- 108010057466 NF-kappa B Proteins 0.000 description 2
- 230000003527 anti-angiogenesis Effects 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- LGQXXHMEBUOXRP-UHFFFAOYSA-N tributyl borate Chemical compound CCCCOB(OCCCC)OCCCC LGQXXHMEBUOXRP-UHFFFAOYSA-N 0.000 description 2
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 229940123407 Androgen receptor antagonist Drugs 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- 206010019695 Hepatic neoplasm Diseases 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000003936 androgen receptor antagonist Substances 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000005040 ion trap Methods 0.000 description 1
- JVTZFYYHCGSXJV-UHFFFAOYSA-N isovanillin Chemical compound COC1=CC=C(C=O)C=C1O JVTZFYYHCGSXJV-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a synthetic antineoplastic, in particular to the synthesis of 4-(4-hydroxy-3-methoxyl benzyl) curcumin and an application thereof for the preparation of the antineoplastic. After 2, 4-pentanedione and vanillin are condensed by Knovenagel, the compound is subjected to catalytic hydrogenation to obtain 3-(4-hydroxy-3-methoxyl benzyl)-2, 4-pentanedione and then the 3-(4-hydroxy-3-methoxyl benzyl)-2, 4-pentanedione and the vanillin are condensed by hydroxyaldehyde to obtain the 4-(4-hydroxy-3-methoxyl benzyl) curcumin. The compound is applied to the preparation of medicaments for the treatment of leukemia, skin cancer, gastric cancer, carcinoma of colon, hepatic carcinoma, breast cancer, prostatic carcinoma or other malignant tumors.
Description
Technical field
The present invention relates to synthesizing antineoplastic medicament, the application that is specifically related to synthetic 4-(4-hydroxy 3-methoxybenzene methyl) curcumine and is used to prepare antitumor drug.
Background technology
Curcumine has the edible and medicinal record of more than one thousand years on India, China, Japan, Korea S and other places.Discover both at home and abroad that at present curcumine has various active such as antitumor, anti-inflammatory, angiogenesis inhibitor, anti-oxidant and neuroprotective.But the curcumine poorly water-soluble, its aqueous solution instability, especially more unstable to the alkaline pH value condition in neutrality, metabolism was fast in vivo after curcumine was oral, and bioavailability is low, and Plasma Concentration is lower, has become the principal element that limits its clinical application.By the synthetic curcumin derivate of structure of modification, enhanced activity, water-soluble significant.Curcumin analogue anti-tumor aspect research at present mainly concentrates on and suppresses the NF-κ B and the AP-1 factor, the in vitro study of anti-angiogenesis activity and androgen antagonist, having of curcumin analogue anti-tumor aspect foreign patent mandate: Vander Jagt etc. uses the NF-κ B and the AP-1 factor is suppressed, screening anti-tumor activity curcumin analogue (US20070060644), the androgen receptor antagonists of Lee etc. (US006790979), the antitumor and anti-angiogenesis activity curcumin analogue (US006664272) of Snyder etc.
Both at home and abroad the structure of modification route to curcumine mainly contains: change substituting group kind and position on the phenyl ring, beta-diketon condensation or unsaturatedly for single ketones, in the middle of changing grip connection chain, reduction unsaturated double-bond, 4 active methylene radical replacements etc. altogether, activity research still is in the experiment in vitro stage.
The present invention is by introducing active structure unit 34 of curcumine parents, and 4-disubstituted benzenes methyl synthesizes new curcumin analogue, and estimates its anti-tumor activity.
Summary of the invention
One of purpose of the present invention is to provide 4-(4-hydroxy 3-methoxybenzene methyl) curcumine, and its structural formula is:
Two of the object of the invention is to provide 4-(4-hydroxy 3-methoxybenzene methyl) preparation method of curcumine.The compounds of this invention 4-(4-hydroxy 3-methoxybenzene methyl) curcumine can be by 2,4-diacetylmethane and Vanillin obtain earlier 3-(4-hydroxy 3-methoxybenzene methylene radical)-2 after the Knovenagel condensation, 4-diacetylmethane (intermediate A), catalytic hydrogenation 3-(4-hydroxy 3-methoxybenzene methylene radical)-2, obtain 3-(4-hydroxy 3-methoxybenzene methyl)-2 behind the 4-diacetylmethane, 4-diacetylmethane (intermediate B), 3-(4-hydroxy 3-methoxybenzene methyl)-2,4-diacetylmethane make 4-(4-hydroxy 3-methoxybenzene methyl) curcumine with Vanillin through aldol condensation again.Its reaction signal formula is as follows:
Three of the object of the invention is to provide 4-(4-hydroxy 3-methoxybenzene methyl) curcumine to be used to prepare the application of antitumor drug.
4-(4-hydroxy 3-methoxybenzene methyl) curcumine can be used for but be not limited to preparation treating leukemia, skin carcinoma, cancer of the stomach, colorectal carcinoma, liver cancer, mammary cancer or prostate cancer medicine.
4-(4-hydroxy 3-methoxybenzene methyl) curcumine can significantly suppress the propagation of various human tumour cell.Can see according to table two, this compound all shows the restraining effect stronger than parent curcumine to seven kinds of cell strains in this experiment, especially this two strains cell strain of K562, B16, this compound is obviously better than the curcumine to their inhibited proliferation, and its half-inhibition concentration is about 1/4 and 1/7 of curcumine.Above result shows that 4-(4-hydroxy 3-methoxybenzene methyl) curcumine tumor cell in vitro inhibited proliferation is stronger than the restraining effect of its parent curcumine.
Embodiment
Synthesizing of embodiment 1 4-(4-hydroxy 3-methoxybenzene methyl) curcumine.
Synthesis material 3-hydroxyl-4-methoxybenzaldehyde (Vanillin), 2,4-diacetylmethane, boron trioxide, tri-n-butyl borate, n-Butyl Amine 99, piperidines are Chemical Reagent Co., Ltd., Sinopharm Group.Catalytic hydrogenation device (U.S. Parr 1100), and nuclear magnetic resonance spectrometer (Unity 500, U.S. Varian company, 500MHz), ion trap mass spectrometer (DECAX-30000, U.S. Thermo Finnigan company); Micro-fusing point instrument (X-4, Shanghai precision instrument factory).
Add 2 in the 250ml single port flask, 4-diacetylmethane 10g (0.1mol), ethanol 100ml adds the catalytic amount piperidines, Vanillin 15g (0.1mol), stirring reaction is 48 hours under the room temperature, concentrates and removes solvent, and recrystallization gets buff powder intermediate A 12.0g.
Add acetone 100ml in the 250ml catalytic hydrogenation bottle, intermediate A 10g, 10% palladium carbon 1g, the pressurized catalysis hydrogenation is 1 hour under the 25PSI, reacting liquid filtering, filtrate concentrates the back recrystallization and gets light brown oily solid intermediate B8.8g.
Intermediate B 2.36g (10mmol) and boron trioxide 0.49g (7mmol) are dissolved among the ethyl acetate 10ml, 40 ℃ of stirring reactions 0.5 hour; Adding Vanillin 3.04g (20mmol),, tri-n-butyl borate 11ml (40.5mmol), stirring reaction is 0.5 hour under the room temperature, splash into the mixed solution of n-Butyl Amine 99 0.2ml (2mmol) and ethyl acetate 10ml, 0.5 hour drip, stirring reaction is 48 hours under the room temperature, adds 0.5M hydrochloric acid 15ml, be warming up to 60 ℃ of reactions 1 hour, the reaction solution ethyl acetate extraction, saturated common salt washing, anhydrous magnesium sulfate drying, concentrate the back ethyl alcohol recrystallization, get orange powder 2.50 grams (productive rate 50%).Mp203-205 ℃, molecular formula C
29H
28O
8,
1H NMR (DMSO) δ (ppm) 3.69 (s, 3H), 3.79 (s, 3H), 3.82 (s, 3H), 3.99 (s, 2H), 6.78 (d, 2H, J=7.5Hz), 6.60-7.27 (m, 9H), 7.58 (d, 2H, J=15.0Hz), 17.9 (s, 1H); ESI-MS (M-H) 503.5.
Embodiment 2 4-(4-hydroxy 3-methoxybenzene methyl) curcumine suppresses tumour cell K562, HL-60, and B-16, SW480, HepG2, MGC80-3, the growth in vitro activity of SH-SY5Y:
2.1. clone
K562: human acute transformation of chronic myelocytic leukemia clone
HL-60: human acute myeloid leukemia cell is
B16: murine melanoma B16 cell strain.
SW480: human colon cancer cell
HepG2: human liver tumor cell
MGC80-3: gastric carcinoma cells
SH-SY5Y: human neuroblastoma cell
Above cell all derives from Chinese Academy of Sciences's Shanghai cell bank.
2.2 cell cultures
The cell cultures liquid formula sees Table 1, and cell is at 37 ℃, 5%CO
2Cultivate in the incubator, the vegetative period cell of taking the logarithm is used for propagation, apoptosis experiment.
Table 1 nutrient solution prescription
2.3 mtt assay is observed the restraining effect of 4-(4-hydroxy 3-methoxybenzene methyl) curcumine on cell proliferation
To be in the cell of logarithmic phase, be that 50000/hole of suspension cell, 8000～12000/hole of attached cell are inoculated in 96 orifice plates by density.Experimental group (attached cell is treated adherent back) adds 4-(4-hydroxy 3-methoxybenzene methyl) curcumine and the curcumine of different concns respectively, not dosing of control group, other establishes blank group and (only adds substratum, acellular), establish three parallel holes for every group, cultivate 48h for 37 ℃, the MTT solution 20ul/ hole that adds 5mg/ml, after continuing to cultivate 4h, the centrifugal supernatant of abandoning adds DMSO150ul, vibration 10min, fully after the cracking, detect absorbancy (OD570) value at 570nm place with full-automatic microplate reader (production of U.S. BIO-RAD company).Calculate inhibitory rate of cell growth according to absorbancy.
Inhibitory rate of cell growth=[control wells OD value-experimental port OD value]/[control wells OD value-blank well OD value] * 100%
To the mapping of growth of tumour cell inhibiting rate, can obtain dose response curve with the different concns of same medicine, obtain the half-inhibition concentration IC50 of this medicine according to equation of linear regression, promptly cell survival rate reduces by 50% o'clock drug level.
2.4 result
4-(4-hydroxy 3-methoxybenzene methyl) curcumine can significantly suppress the propagation of various human tumour cell, according to table 2, we can see, this compound all shows the restraining effect stronger than parent curcumine to seven kinds of cell strains in this experiment, especially this two strains cell strain of K562, B16, this compound is obviously better than the curcumine to their inhibited proliferation, and its half-inhibition concentration is about 1/4 and 1/7 of curcumine.Above result shows that 4-(4-hydroxy 3-methoxybenzene methyl) curcumine tumor cell in vitro inhibited proliferation is stronger than the restraining effect of its parent curcumine.
Table 2
4-(4-hydroxy 3-methoxybenzene methyl) curcumine and curcumine are to the inhibited proliferation of cultured cell in vitro
Claims (4)
- (1.4-4-hydroxy 3-methoxybenzene methyl) curcumine, its structural formula is:
- 2. the preparation method of the described 4-of claim 1 (4-hydroxy 3-methoxybenzene methyl) curcumine, comprise the steps: by 2,4-diacetylmethane and Vanillin obtain earlier 3-(4-hydroxy 3-methoxybenzene methylene radical)-2 after the Knovenagel condensation, the 4-diacetylmethane, catalytic hydrogenation 3-(4-hydroxy 3-methoxybenzene methylene radical)-2, obtain 3-(4-hydroxy 3-methoxybenzene methyl)-2 behind the 4-diacetylmethane, the 4-diacetylmethane, 3-(4-hydroxy 3-methoxybenzene methyl)-2,4-diacetylmethane make 4-(4-hydroxy 3-methoxybenzene methyl) curcumine with Vanillin through aldol condensation again.
- 3. the described 4-of claim 1 (4-hydroxy 3-methoxybenzene methyl) curcumine is used to prepare the application of antitumor drug.
- 4. 4-as claimed in claim 3 (4-hydroxy 3-methoxybenzene methyl) curcumine is used to prepare the application of antitumor drug, it is characterized in that: described antitumor drug is the medicine of treatment leukemia, skin carcinoma, cancer of the stomach, colorectal carcinoma, liver cancer, mammary cancer, prostate cancer or other malignant tumours.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101570496B (en) * | 2009-06-12 | 2012-08-15 | 乐山师范学院 | Curcumin-4-nitrogen-containing derivatives, and preparation method and uses thereof |
| CN104030904A (en) * | 2014-03-07 | 2014-09-10 | 福建医科大学 | Application of 4-arylmethyl curcumin analogues serving as Hsp90 inhibitor |
| US9402834B2 (en) | 2014-10-21 | 2016-08-02 | Ions Pharmaceutical S.À R.L. | Human therapeutic agents |
| US9907786B2 (en) | 2014-10-21 | 2018-03-06 | Ions Pharmaceutical S.À R.L. | Therapeutic compositions containing harmine and isovanillin components, and methods of use thereof |
| US10092550B2 (en) | 2014-10-21 | 2018-10-09 | Ions Pharmaceutical S.À R.L. | Therapeutic compositions containing curcumin, harmine, and isovanillin components, and methods of use thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003515590A (en) * | 1999-12-03 | 2003-05-07 | エモリー ユニバーシティ | Curcumin analogs for treating cancer |
| US6790979B2 (en) * | 2002-04-17 | 2004-09-14 | University Of North Carolina At Chapel Hill | Curcumin analogues and uses thereof |
| US7355081B2 (en) * | 2002-04-17 | 2008-04-08 | The University Of North Carolina At Chapel Hill | Curcumin analogues and uses thereof |
| CN101003470B (en) * | 2007-01-22 | 2011-11-02 | 温州医学院生物与天然药物开发中心有限公司 | Analog of mono carbonyl structure of curcumin, and usage |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101570496B (en) * | 2009-06-12 | 2012-08-15 | 乐山师范学院 | Curcumin-4-nitrogen-containing derivatives, and preparation method and uses thereof |
| CN104030904A (en) * | 2014-03-07 | 2014-09-10 | 福建医科大学 | Application of 4-arylmethyl curcumin analogues serving as Hsp90 inhibitor |
| US9402834B2 (en) | 2014-10-21 | 2016-08-02 | Ions Pharmaceutical S.À R.L. | Human therapeutic agents |
| US9907786B2 (en) | 2014-10-21 | 2018-03-06 | Ions Pharmaceutical S.À R.L. | Therapeutic compositions containing harmine and isovanillin components, and methods of use thereof |
| US10092550B2 (en) | 2014-10-21 | 2018-10-09 | Ions Pharmaceutical S.À R.L. | Therapeutic compositions containing curcumin, harmine, and isovanillin components, and methods of use thereof |
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