Synthesis and cytotoxic analysis of some disodium 3beta,6beta-dihydroxysterol disulfates.
Disodium 3beta,6beta-dihydroxy-5alpha-cholestane disulfate (1) was synthesized in 4 steps with a high overall yield from cholesterol. First, cholesterol (4a) was converted to cholest-4-en-3,6-dione (5a) via oxidation with pyridinium chlorochromate (PCC) and then 5a was reduced by NaBH(4) in the presence of NiCl(2) to produce cholest-3beta,6beta-diol (6a). The reaction of 6a with the triethylamine-sulfur trioxide complex generated diammonium 3beta,6beta-dihydroxy-5alpha-cholestane disulfate (7a) and the treatment of 7a by cation exchange resin 732 (sodium form)(Na(+)) yielded the target steroid 1. Disodium 24-ethyl-3beta,6beta-dihydroxycholest-22-ene disulfate (2) and disodium 24-ethyl-3beta,6beta-dihydroxycholestane disulfate (3) were synthesized using a similar method. The cytotoxicity of these compounds against Sk-Hep-1 (human liver carcinoma cell line), H-292 (human lung carcinoma cell line), PC-3 (human prostate carcinoma cell line) and Hey-1B (human ovarian carcinoma cell line) cells was investigated. Our results indicate that presence of a cholesterol-type side chain at position 17 is necessary for their biological activity.
Cui
Jianguo
J
College of Chemistry and Life Science, Guangxi Teachers Education University, Nanning, China. cuijg1954@126.com
Wang
Hui
H
Huang
Yanmin
Y
Xin
Yi
Y
Zhou
Aimin
A
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002777:Cholestanols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002784:Cholesterol / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology
D000970:Antineoplastic Agents; D002777:Cholestanols; D002784:Cholesterol