CN103044514A - Preparation method of 3beta-hydroxy-6-thiosemicarbazone steroid metal complex and application of metal complex in antineoplastic drug - Google Patents
Preparation method of 3beta-hydroxy-6-thiosemicarbazone steroid metal complex and application of metal complex in antineoplastic drug Download PDFInfo
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Abstract
The invention discloses a 3beta-hydroxy-6-thiosemicarbazone steroid metal complex having a different branched chain structure. A chemical structural formula of the metal complex is as Formula I as shown in the specification, wherein M in Formula I is Pt (II) and Cu (II). The 3-hydroxy-6-thiosemicarbazone steroid metal complex with the different branched chain structure is obtained by starting from cholesterol, sitosterol or stigmasterol, performing pyridinium chlorochromate oxidization, and sodium borohydride selective reduction, then performing 6-carbonyl functional group transformation, and further performing metal ion coordination. An experiment proves that the 3-hydroxy-6-thiosemicarbazone steroid metal complex with the different branched chain structure has an obvious inhibition effect on various tumor cell strains, and can be applied in preparing a drug for treating a cancer.
Description
One, technical field
The present invention relates to synthetic method and the application in the preparation antitumor drug thereof of 3 beta-hydroxies that a class has different branched structures-6-amithiozone steroidal metal complexes.
Two, background technology
Cancer (medically the malignant tumour that derives from epithelium being called cancer) is to one of human health and the dangerous maximum disease of quality of life.Seeking efficient, highly selective and the little cancer therapy drug of side effect is the main direction of cancer therapy drug exploitation.In the research of antitumor drug, once reported steroidal metal complexes (Juan M.Fern á ndez G., Manuel F.Rubio-Arroyo, Consuelo Rubio-Poo, Aurora de la that steroid nucleus and metal pharmacophoric group directly link to each other
Palladium (II) and Platinum (II) Dichloro Complexes Containing Diamine-estrone Derivatives[J] Monatsh.Chem., 1983,114 (5), 535 – 540; Minas P.Georgiadis, Serkos A.Haroutounian, KostasP.Chondros; Synthesis and Biological Studies of Steroidal cis-Platinum (II) Complexes[J] Inorg.Chim.Acta, 1987,138 (3), 249-252.; Y. Kidani, K.Suzuki, M, Noji, T.Tashiro; Antitumor Activity of Steroid-containing Platinum (II) Complexes of1R, 2R-CycIohexanediamine and2-(Aminomethyl)-cyclohexylamine Isomers Against Leukemia L1210[J] Biomed. ﹠amp; Pharmcother., 1989,43 (4), 261-264.), steroid nucleus and metal pharmacophoric group the steroidal metal complexes (Ottavio Gandolfi, Michael Cais, the Giuliano Dolcetti that link to each other by connexon, Mauro Ghedini, Alfred Modinao; Metalloimmunoassay.V. Steroid-Platinum (II) o-Catecholato Complexes:A Novel Set of Metalloptens[J] Inorg.Chim.Acta, 1981,56,127-133; Ottavio Gandolfi, Jochanan Blum, Frederike Mandelbaum-Shavit; Antitumor Steroid-cis-Platinum (II)-o-Catecholato Conjugates:Preliminary Evaluation on Breast Cancer MCF-7Cells[J] Inorg.Chim.Acta, 1984,91 (4), 257-261.Above-claimed cpd has significant inhibition growth increment effect external to some tumour cell.
200810073497.4) and the application for a patent for invention (Chinese patent: 201010107528.0) of " 6-replacement-4-azepine-A-homo-3-oxo steroidal compounds and in the application of preparation in the antitumor drug " we once provided a class " 3; 6-di-substituted sterides oxime compounds is as antitumor drug " (Chinese patent:, and be relevant report (Jian-Guo Cui, Lei Fan, Li-Liang Huang, Hong-Li Liu, Ai-Min Zhou.Steroids, 2009,74 (1), 62-72; Jianguo Cui, Lei Fan, Yanmin Huang, Yi Xin, Aimin Zhou, Steroids.2009,74 (12), 989-995; Yanmin Huang, Sijing Chen, Jianguo Cui, Chunfang Gan, Zhiping Liu, Yingliang Wei, Huachan Song.Steroids2011,76:690 – 694; Yanmin HUANG, Jianguo CUI, Zhengguo ZHONG, Chunfang GAN, Wenyan ZHANG, Huacan SONG, Bioorg.Med.Chem.Lett.2011,21:3641 – 3643; Yanmin HUANG, Jianguo CUI, Sijing CHEN, Chunfang GAN, Aimin ZHOU, Steroids76 (2011) 1346 – 1350.).
(3) summary of the invention
The purpose of this invention is to provide 3 beta-hydroxies that a class has different branched structures-6-amithiozone steroidal metal complexes.
Another object of the present invention provides the synthetic method of above-claimed cpd.
Further purpose of the present invention provides the application of above-claimed cpd in the preparation antitumor drug.
The present invention is achieved through the following technical solutions above-mentioned purpose: a class has 3 beta-hydroxies of different branched structures-6-amithiozone steroidal metal complexes, and its chemical structural formula is suc as formula shown in the I:
The formula I
M=Pt(II wherein), Cu(II).
One class has 3 beta-hydroxies of different branched structures-6-amithiozone steroidal metal complexes, these metal complexess are 3 beta-hydroxy courage steroids-6-amithiozone metal complexes (1), 3 beta-hydroxy paddy steroids-6-amithiozone metal complexes (2), 3 beta-hydroxy beans steroids-6-amithiozone metal complexes (3), and structural formula is:
M=Pt(II wherein), Cu(II).
The method for preparing described metal complexes, the method is from cholesterol, be oxidized to the courage Gona-4-ene-3 through pyridinium chlorochromate first, the 6-diketone, then under the katalysis of nickelous chloride, use the sodium borohydride selective reduction to become 3 beta-hydroxy courage steroid-6-ketone, further 6-position carbonyl is carried out functional group's conversion, obtain 3 beta-hydroxy courage steroid-6-amithiozones, last and metallic ion coordination obtains 3 beta-hydroxy courage steroids-6-amithiozone steroidal metal complexes, 3 beta-hydroxy paddy steroids-6-amithiozone steroidal metal complexes, 3 beta-hydroxy beans steroids-6-amithiozone steroidal metal complexes synthetic respectively take Sitosterol and Stigmasterol as initial feed being adopted the preparation that uses the same method synthetic.
The application of described 3 beta-hydroxies with different branched structures-6-amithiozone steroidal metal complexes in the preparation antitumor drug.
Described 3 beta-hydroxies with different branched structures-6-amithiozone steroidal metal complexes is the application of medicinal compositions in the preparation antitumor drug of activeconstituents.
From cholesterol, press following chemical equation synthesising target compound:
M=Pt(II wherein), Cu(II).
Show by vitro inhibition growth of cancer cells increment activity test, 3 beta-hydroxies with different branched structures of the present invention-6-amithiozone steroidal metal complexes has significant restraining effect to cancer cell strains such as various tumor cell strains such as cancer of the stomach, cervical cancer, liver cancer, prostate cancer, nasopharyngeal carcinoma and lung cancer.Simultaneously, the anti-tumor activity experiment shows in the animal body, and 3 beta-hydroxies with different branched structures of the present invention-6-amithiozone steroidal metal complexes has certain restraining effect to prostate cancer.Therefore metal complexes of the present invention can be used in the preparation antitumor drug
Four, embodiment
The invention will be further described by the following examples.
Embodiment 1
The preparation of 3 beta-hydroxy courage steroids-6-amithiozone metal complexes
The courage Gona-4-ene-3,6-diketone (1a):
In the 50mL reaction flask, add the 0.386g cholesterol, methylene dichloride 40mL, disposable adding PCC1.3g, the rapid blackening of solution.Stir 48h under the room temperature, the TLC monitoring, developping agent is: ethyl acetate: sherwood oil=1:4, without stopped reaction behind the raw material point.Reactant inclines into a silica gel short column, ethyl acetate rinse, with saturated sodium bicarbonate solution, water, saturated common salt washing, anhydrous sodium sulfate drying filters elutant respectively, decompression steams solvent, thick product column chromatography for separation, eluent is ethyl acetate: sherwood oil=1:6, obtains the little yellow solid product 1a of 0.355g, productive rate 89%, m.p.90 ~ 91 ℃; IR, KBr compressing tablet, ν/cm
-1: 2953,2865,1693,1600,1486,1249,1221,1117,942;
1H NMR (CDCl
3, 500MHz) δ: 0.746 (3H, s, 18-CH
3), 0.886 (3H, d, J=6.4Hz, 26or27-CH
3), 0.899 (3H, d, J=6.4Hz, 26or27-CH
3), 0.952 (3H, d, J=6.5Hz, 21-CH
3), 1.172 (3H, s, 19-CH
3), 2.546 (1H, dd, J=14.6Hz and 5.2Hz, C
2-β H), 2.706 (1H, dd, J=16.0Hz and 4.0Hz, C
7-α H), 6.196 (1H, s, C
4-H).
Synthetic (2a) of 3 beta-hydroxy courage steroid-6-ketone:
119mg compound 1a and 71mg NiCl
26H
2O is dissolved in the 15mL methyl alcohol, behind the stirring 15min, adds 35mg NaBH in 5min in batches
4, react with the cancellation of 1N hydrochloric acid behind the reaction 5min.The most of methyl alcohol of pressure reducing and steaming adds 15mL water, has a large amount of white precipitates to produce, and uses 15mL ethyl acetate extraction three times, and extraction liquid is washed to neutrality with saturated common salt, anhydrous sodium sulfate drying.Filter pressure reducing and steaming solvent, thick product column chromatography for separation, moving phase: V
Sherwood oil: V
Ethyl acetate=4:1 gets white solid product 2a87mg.Productive rate 72%, m.p.161 ~ 162 ℃; The spectroscopic data of compound 2a: IR, KBr compressing tablet ν/cm
-1: 3378,2937,2864,1711,1466,1384,1262,1172,1021,959,796;
1H NMR (CDCl
3, 500MHz) δ: 0.71 (3H, s, 18-CH
3), 0.89 (6H, d, J=2.3,2.3Hz, 26 and 27-CH
3), 0.93 (3H, d, J=6.4Hz, 21-CH
3), 1.02 (3H, s, 19-CH
3), 2.02 (2H, dd, J=13.1,11.0Hz, 7-CH
2), 3.77 (1H, br.s, 3-CH).
Synthetic (3a) of 3 beta-hydroxy courage steroid-6-amithiozones:
Get 100mg compound 2a and be dissolved in the 20mL dehydrated alcohol, splashing into Glacial acetic acid regulator solution pH value behind the dissolve complete is 3 ~ 5, keeps 70 ℃ of temperature of reaction, adds the 27mg thiosemicarbazide behind the stirring 10min, the TLC monitoring, and developping agent is: V
Sherwood oil: V
Ethyl acetate=1:1 continues reaction 6h, without stopped reaction behind the raw material point.The most of ethanol of pressure reducing and steaming adds suitable quantity of water, uses 10mL ethyl acetate extraction three times, and organic phase is washed till neutrality with saturated NaCl, anhydrous sodium sulfate drying.Filter pressure reducing and steaming solvent, thick product column chromatography for separation moving phase: V
Sherwood oil: V
Ethyl acetate=2:1 gets white solid product 3a78mg, productive rate 65%.M.p.259 ~ 261 ℃; The spectroscopic data of compound 3a: IR KBr compressing tablet, ν/cm
-1: 3432,2929,2864,1662,1580,1466,1384,1066;
1H NMR (CDCl
3, 300MHz) δ: 0.669 (s, 3H, 18-CH
3), 0.717 (s, 3H, 19-CH
3), 0.892 (d, 6H, J=4.3Hz, 26-CH
3Or 27-CH
3), 1.151 (d, 3H, J=5.3Hz, 21-CH
3), 3.640 (m, 1H, 3-CH), 6.330 (s, 1H ,-NH
2), 7.251 (s, 1H ,-NH
2), 8.751 (s, 1H ,-NH);
13C NMR (CDCl
3, 75MHz) δ: 35.7 (1-C), 31.0 (2-C), 71.0 (3-C), 39.5 (4-C), 51.1 (5-C), 155.5 (6-C), 31.5 (7-C), 31.7 (8-C), 54.3 (9-C), 36.6 (10-C), 18.7 (11-C), 39.5 (12-C), 43.1 (13-C), 56.4 (14-C), 23.8 (15-C), 28.1 (16-C), 56.1 (17-C), 12.1 (18-C), 24.2 (19-C), 36.1 (20-C), 12.7 (21-C), 36.4 (22-C), 22.8 (23-C), 39.7 (24-C), 28.0 (25-C), 21.5 (26-C), 22.6 (27-C), 179.1 (C=S).
Dichloro [3 beta-hydroxy courage steroid-6-amithiozone-N, S] closes synthetic (4a) of platinum (II):
0.060g compound 16 is placed the round-bottomed flask that is connected with spherical condensation tube, adding 5mL methyl alcohol and chloroform volume ratio is the solution of 1:1, stirring and dissolving under 70 ° of C of oil bath, and behind dissolve complete, rapid disposable adding 0.058g K
2PtCl
4, continue 70 ° of C back flow reaction.Stopped reaction behind the 10h is cooled to room temperature, filters, and obtains glassy yellow precipitation and yellow filtrate, uses successively ethyl acetate, methyl alcohol, methylene dichloride, distilled water wash precipitation.Vacuum-drying gained precipitation under 45 ° of C obtains 0.061g glassy yellow pulverulent solids product 17, productive rate: 52%, and fusing point: 344 ~ 346 ° of C.IR(KBr)
3432,2933,2864,1634,1384,1078,600;
1H?NMR(300MHz,DMSO-d
6)δ:0.631(s,3H,18-CH
3),0.859(s,6H,26-?&?27-CH
3),2.928(s,1H,3-CH),8.103(s,1H,-NH
2),8.895(s,1H,-NH
2),11.117(s,1H,-NH);
13C?NMR(75MHz,DMSO-d
6)δ:69.75(3-C),164.95(6-C),186.87(C=S);MS(ESI,Positive)m/z:822.37(M+DMSO+H).
Dichloro [3 beta-hydroxy courage steroid-6-amithiozone-N, S] closes synthetic (5a) of copper (II):
0.080g compound 16 is placed the round-bottomed flask that is connected with spherical condensation tube, adding 5mL methyl alcohol and chloroform volume ratio is the solution of 1:1, stirring and dissolving under 70 ° of C of oil bath, and behind dissolve complete, rapid disposable adding 0.034g CuCl
22H
2O continues 70 ° of C back flow reaction.Stopped reaction behind the 4h is cooled to room temperature, filters, and obtains gray precipitate and yellow filtrate, uses successively ethyl acetate, methyl alcohol, methylene dichloride, distilled water wash precipitation.Vacuum-drying gained precipitation under 45 ° of C obtains 0.063g gray powder powder solid product 18, productive rate: 55%, and fusing point: 287 ~ 289 ° of C.IR(KBr)
3423,2953,2868,1625,1384,1078;
1H?NMR(300MHz,CDCl
3)δ:0.676(s,3H,18-CH
3),7.167(s,1H,-NH
2),8.352(s,1H,-NH
2),10.284(s,1H,-NH);
13C?NMR(75MHz,CDCl
3)δ:70.97(3-C),163.04(6-C),170.92(C=S).
Embodiment 2
The preparation of 3 beta-hydroxy paddy steroids-6-amithiozone metal complexes
The paddy Gona-4-ene-3, synthetic (1b) of 6-diketone:
Synthetic method and courage Gona-4-ene-3, the synthetic method of 6-diketone is identical.The paddy Gona-4-ene-3, the productive rate 83% of 6-diketone (1b); M.p.171 ~ 173 ℃.The spectroscopic data of compound 1b: IR (KBr) ν/cm
-1: 2954,2864,1683,1601,1581,1461,1377,1246,1217,1124,948;
1H NMR (500MHz, CDCl
3) δ: 0.735 (s, 3H, 18-CH
3), 0.828 (d, 3H, J=7.0Hz, 26-CH
3), 0.850 (d, 3H, J=7.3Hz, 27-CH
3), 0.858 (t, 3H, J=7.6Hz, 29-CH
3), 0.946 (d, 3H, J=6.3Hz, 21-CH
3), 1.176 (s, 3H, 19-CH
3), 2.673 (dd, 1H, J=16.0,3.5Hz, 7-C
αH), 6.176 (s, 1H, 4-CH).
Synthetic (2b) of 3 beta-hydroxy paddy steroid-6-ketone:
Synthetic method is identical with the synthetic method of 3 beta-hydroxy courage steroid-6-ketone.Productive rate: 47%.Fusing point: 124 ~ 125 ° of C(literature values: 118 ~ 120 ° of C).
Synthetic (3b) of 3 beta-hydroxy paddy steroid-6-amithiozones:
Synthetic method is identical with the synthetic method of 3 beta-hydroxy courage steroid-6-amithiozones.Productive rate: 68%.Fusing point: 256 ~ 257C.
1H?NMR(300MHz,CDCl3)δ:0.646(s,3H,18-CH3),0.697(s,3H,19-CH3),2.646(s,1H,5-CH),2.684(s,H,3-OH),0.646(s,3H,18-CH3),6.654(m,1H,-NH2),7.271(m,1H,-NH2),8.885(s,1H,-NH);
13C?NMR(75MHz,CDCl
3)δ:70.92(3-C),155.78(6-C),178.75(C=S);
Dichloro [3 beta-hydroxy paddy steroid-6-amithiozone-N, S] closes synthetic (4b) of platinum (II):
The synthetic method that synthetic method and dichloro [3 beta-hydroxy beans steroid-6-amithiozone-N, S] close platinum (II) is identical.Productive rate 44%.Fusing point: 348 ~ 350 ° of C.IR(KBr)ν/cm-1:3427,2929,2864,1617,1388,1061;1H?NMR(300MHz,DMSO-d6)δ:8.120(s,1H,-NH2),8.900(s,1H,-NH2),11.122(s,1H,-NH);MS(ESI,Negative)m/z:846.40(M+DMSO-H);
Dichloro [3 beta-hydroxy paddy steroid-6-amithiozone-N, S] closes synthetic (5b) of copper (II):
The synthetic method that synthetic method and dichloro [3 beta-hydroxy beans steroid-6-amithiozone-N, S] close copper (II) is identical.Productive rate 44%.Fusing point: 279 ~ 281 ° of C.
1H?NMR(300MHz,DMSO-d6)δ:7.715(s,1H,-NH2),8.672(s,1H,-NH2),10.693(s,1H,-NH).
Embodiment 3
The preparation of 3 beta-hydroxy beans steroids-6-amithiozone metal complexes
The beans Gona-4-ene-3, synthetic (1c) of 6-diketone
Synthetic method and courage Gona-4-ene-3, the synthetic method of 6-diketone is identical.The beans Gona-4-ene-3, the productive rate 81% of 6-diketone (1c); M.p.152 ~ 153 ℃.The spectroscopic data of compound 1c: IR (KBr) ν/cm
-1: 2953,2868,1687,1679,1458,1384,1245,1221,1119,972;
1H NMR (500MHz, CDCl
3) δ: 0.758 (s, 3H, 18-CH
3), 0.814 (d, 3H, J=7.0Hz, 26-CH
3), 0.822, (t, 3H, J=7.4Hz, 29-CH
3), 0.863 (d, 3H, J=6.5Hz, 27-CH
3), 1.051 (d, 3H, J=6.5Hz, 21-CH
3), 1.183 (s, 3H, 19-CH
3), 2.168 (m, 1H, 7-C
βH), 2.496 (m, 1H, 2-C
αH), 2.590 ~ 2.516 (m, 1H, 2-C
βH), 2.690 (dd, 1H, J=16.0,4.5Hz, 7-C
αH), 5.057 (dd, 1H, J=15.1,8.6Hz, 22-CH), 5.167 (dd, 1H, J=15.1,8.6Hz, 23-CH), 6.183 (s, 1H, 4-CH).
Synthetic (2c) of 3 beta-hydroxy beans steroid-6-ketone:
0.496g compound 1c and 0.274g NiCl26H2O are dissolved in the 40mL methyl alcohol.Under 35 ° of C water-baths, stir 15 min, then in 5 minutes, add 0.150gNaBH4 in batches, react with the cancellation of 1N hydrochloric acid behind the reaction 15min, the most of methyl alcohol of pressure reducing and steaming, add 15mL water, have a large amount of white precipitates to produce, use ethyl acetate extraction, extraction liquid is washed to neutrality with saturated common salt, anhydrous slufuric acid is dry, filter, the pressure reducing and steaming solvent gets white thick product.Thick product is through column chromatography for separation, and eluent is: the V ethyl acetate: V sherwood oil=1:4 gets 0.272g white solid 2c, productive rate 54.3%.Fusing point: 143 ~ 145 ° of C, [4] 146 ~ 147 ° of C of literature value.IR(KBr)ν/cm-1:3411,2958,2864,1707,1458,1380,1229,1066,963;1H?NMR(500MHz,CDCl3)δ:0.702(s,3H,18-CH3),0.779(s,3H,19-CH3),0.812(d,3H,J=6.0Hz,26-CH3),0.821(t,3H,J=7.5Hz,29-CH3),0.862(d,3H,J=6.0Hz,27-CH3),1.041(d,3H,J=6.5Hz,21-CH3),2.230(dd,1H,J1=12.5Hz,J2=2.0Hz,7β-CH),2.239(dd,1H,J1=13.5Hz,J2=4.5Hz,7α-CH),3.599(m,1H,3α-CH),5.040(dd,1H,J1=15.6Hz,J2=8.5Hz,23-CH),5.158(dd,1H,J=15.5,8.6Hz,22-CH).
Synthetic (3c) of 3 beta-hydroxy beans steroid-6-amithiozones:
Synthetic method is identical with the synthetic method of 3 beta-hydroxy courage steroid-6-amithiozones.Productive rate: 76%.Fusing point: fusing point: 234 ~ 235 ° of C.
1H?NMR300MHz,DMSO-d6，δ:0.677(s,3H,18-CH3),3.322(m,1H,3-CH),6.911(s,1H,-NH2),7.281(s,1H,-NH2),8.941(s,1H,-NH).
Dichloro [3 beta-hydroxy beans steroid-6-amithiozone-N, S] closes synthetic (4c) of platinum (II):
The synthetic method that synthetic method and dichloro [3 beta-hydroxy beans steroid-6-amithiozone-N, S] close platinum (II) is identical.Productive rate 44%.Fusing point: 318 ~ 320 ° of C; IR KBr compressing tablet ν/cm-1:3509,3399,3264,3129,2949,2864,1629,1556,1388,1070; 1H NMR (300MHz, DMSO-d6) δ: 5.098 (m, 22-﹠amp; 23-CH), 8.110 (s, 1H ,-NH2), 8.913 (s, 1H ,-NH2), 11.118 (s, 1H ,-NH); 13C NMR (75MHz, DMSO-d6) δ: 168.83 (C=S), 164.96 (6-C), 138.43 (22-C), 129.37 (23-C), 69.74 (3-C); MS (ESI, Negative) m/z:844.42 (M+DMSO-H);
Dichloro [3 beta-hydroxy beans steroid-6-amithiozone-N, S] closes synthetic (5c) of copper (II):
The synthetic method that synthetic method and dichloro [3 beta-hydroxy beans steroid-6-amithiozone-N, S] close copper (II) is identical.Productive rate 50%.Fusing point: 252 ~ 253 ° of C; IR (KBr) ν/cm-1:3509,3277,3154,2959,2859,1601,1531,1388,1045; 1HNMR (300MHz, DMSO-d6) δ: 5.066 (m, 22-﹠amp; 23-CH), 7.797 (s, 1H ,-NH2), 8.708 (s, 1H ,-NH2), 10.734 (s, 1H ,-NH); MS (ESI, Positive) m/z:657.42 (M+Na-H);
Embodiment 4
The present embodiment is to adopt 3 beta-hydroxies with different side chains of the present invention-6-amithiozone steroidal metal complexes tumour cell to be carried out the test result of cell toxicity test.
Adopt 3 beta-hydroxies with different side chains of the present invention-6-amithiozone steroidal metal complexes to human nasopharyngeal epithelioma 1 GNE2, lung cancer cell line SPC-A, ovarian cancer Hey-1B, prostatic cell PC-3, Tramp C1, Du145 breast cancer cell SKBR3 and people's epidermis lung carcinoma cell H292 carry out cell toxicity test.Adopt the MTT method, carry out vitro cytotoxicity and measure.3 beta-hydroxies with different side chains of adding different concns-6-amithiozone steroidal metal complexes in the logarithmic phase cell of in 96 orifice plates, cultivating, carry out simultaneously 3 parallel tests, compare with control group, cultivate after 72 hours, add MTT, measure its absorbancy, the concentration of compound when calculating respectively inhibition tumor cell and growing into 50% is with IC
50Value representation.The result shows that the compound of this type has good anti tumor activity in vitro, and dichloro [3 beta-hydroxies androstane-5-alkene-17-amithiozone-N, S] closes platinum (II) nasopharyngeal carcinoma cell GNE2 is had preferably cytotoxicity, IC
50Value is 20 μ mol/L.Compound dichloro [3 beta-hydroxy courage steroid-6-amithiozone-N, S] closes copper and various types of cells is all had a lot of anti-tumor activities, result such as following table:
Table 1 dichloro [3 beta-hydroxy courage steroid-6-amithiozone-N, S] closes copper to the IC of all kinds of tumour cell anti-tumor activities
50(μ mol/L)
| Cell strain | Hey-1B | SPC-A | CNE2 | PC-3 | H292 | SKBR3 | Tramp?C1 | Du145 |
| IC 50 | 0.5 | 31 | 4.0 | 12.5 | 31.2 | 8.8 | 16 | 22 |
As can be seen from Table 1, to close copper very good to the restraining effect of ovarian cancer (Hey-1B) cell for compound dichloro [3 beta-hydroxy courage steroid-6-amithiozone-N, S].Simultaneously, the anti-tumor activity experiment shows in the animal body, and compound 5a has obvious restraining effect to prostate cancer, ovarian cancer.
Claims (5)
1. a class has 3 beta-hydroxies of different branched structures-6-amithiozone steroidal metal complexes, and its chemical structural formula is suc as formula shown in the I:
The formula I
M=Pt(II wherein), Cu(II).
2. a class has 3 beta-hydroxies of different branched structures-6-amithiozone steroidal metal complexes, it is characterized in that, these metal complexess are 3 beta-hydroxy courage steroids-6-amithiozone metal complexes (1), 3 beta-hydroxy paddy steroids-6-amithiozone metal complexes (2), 3 beta-hydroxy beans steroids-6-amithiozone metal complexes (3), and structural formula is:
M=Pt(II wherein), Cu(II).
3. a class as claimed in claim 1 has the preparation method of 3 beta-hydroxies of different branched structures-6-amithiozone steroidal metal complexes, it is characterized in that, the method is from cholesterol, be oxidized to the courage Gona-4-ene-3 through pyridinium chlorochromate first, the 6-diketone, then under the katalysis of nickelous chloride, use the sodium borohydride selective reduction to become 3 beta-hydroxy courage steroid-6-ketone, further 6-position carbonyl is carried out functional group's conversion, obtain 3 beta-hydroxy courage steroid-6-amithiozones, last and metallic ion coordination obtains 3 beta-hydroxy courage steroids-6-amithiozone steroidal metal complexes, 3 beta-hydroxy paddy steroids-6-amithiozone steroidal metal complexes, 3 beta-hydroxy beans steroids-6-amithiozone steroidal metal complexes synthetic respectively take Sitosterol and Stigmasterol as initial feed being adopted the preparation that uses the same method synthetic.
4. the application of 3 beta-hydroxies with different branched structures as claimed in claim 1-6-amithiozone steroidal metal complexes in the preparation antitumor drug.
5. 3 beta-hydroxies with different branched structures as claimed in claim 1-6-amithiozone steroidal metal complexes is the application of medicinal compositions in the preparation antitumor drug of activeconstituents.
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| CN103254266A (en) * | 2013-05-19 | 2013-08-21 | 广西师范学院 | Steroid zinc metal complex and preparation method thereof as well as application of complex in preparation of antitumor medicines |
| CN105461781A (en) * | 2015-12-17 | 2016-04-06 | 华南理工大学 | Tea sapogenin zinc complex and preparation method as well as use thereof |
| WO2023179721A1 (en) * | 2022-03-25 | 2023-09-28 | 苏州恩泰新材料科技有限公司 | 7-ketolithocholic acid intermediate, synthesis method therefor, and application thereof |
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| CN101245090A (en) * | 2008-03-14 | 2008-08-20 | 广西师范学院 | 3,6-di-substituted sterides oximes compound as antineoplastic medicament |
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| CN101245090A (en) * | 2008-03-14 | 2008-08-20 | 广西师范学院 | 3,6-di-substituted sterides oximes compound as antineoplastic medicament |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103254266A (en) * | 2013-05-19 | 2013-08-21 | 广西师范学院 | Steroid zinc metal complex and preparation method thereof as well as application of complex in preparation of antitumor medicines |
| CN103254266B (en) * | 2013-05-19 | 2016-04-13 | 广西师范学院 | Steroidal zinc metal complexes and preparation method thereof and the application in the anti-gastric cancer medicament of preparation |
| CN105461781A (en) * | 2015-12-17 | 2016-04-06 | 华南理工大学 | Tea sapogenin zinc complex and preparation method as well as use thereof |
| WO2023179721A1 (en) * | 2022-03-25 | 2023-09-28 | 苏州恩泰新材料科技有限公司 | 7-ketolithocholic acid intermediate, synthesis method therefor, and application thereof |
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