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Novel modified steroid derivatives of androstanolone as chemotherapeutic anti-cancer agents

pharmacy 添加于 2009-9-18 23:03 | 1402 次阅读 | 0 个评论

作者
El-Far M, Elmegeed GA, Eskander EF, Rady HM, Tantawy MA
摘要
The aim of the present study is to synthesize and evaluate new potential chemotherapeutic anti-tumor agents. Several thiazolo-, pyrido-, pyrano- and lactam steroid derivatives were obtained using 17 beta-hydroxy-5 alpha-androstan-3-one (androstanolone) 1 as starting steroid. The structure of the novel steroid derivatives was confirmed using the analytical and spectral data. The most pure and structurally promising compounds 7a,10a, 126, 18 and 23 were evaluated as anti-tumor agents. The in vitro cytotoxic activity was evaluated against hepatoma cell lines using MTT assay. Also the in vivo anti-tumor activity was evaluated against Ehrlich ascites carcinoma (EAC). The results of the in vitro study showed that at incubation time 72 h, in olive oil, compound 7a was the most effective cytotoxic compound with IC50 of 30 mu M, while the effects of compounds 18 and 23 were approximately similar with IC50 of 37 PM and 35 mu M respectively. While the tested compounds when dissolved in DMSO showed approximately the same IC50 at both 48 and 72 h incubation period, compound 23 was the most effective cytotoxic with IC50 42 mu M at 48 h and 40 mu M at 72 h. The results of the in vivo study showed that all the tested novel compounds at 25 mg/kg were effective against EAC. Our novel steroid derivatives are promising candidates as anti-cancer agents, none of the mice treated with our novel derivatives showed any toxic symptoms, but they also completely inhibited tumor growth and retained the hemoglobin content, body weight, and WBCs near normal values and similar to what obtained for the standard drug 5-flurouracil. (C) 2009 Elsevier Masson SAS. All rights reserved.
详细资料
- 关键词: Anti-tumor; Steroids; Heterocycles; Hepatoma (HepG(2)); Ehrlich ascites carcinoma (EAC); Cytotoxicity
- 文献种类:期刊
- 期刊名称: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
- 期卷页: 2009年第44卷第10期 3936-3946页
- 出版社: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 23 RUE LINOIS, 75724 PARIS, FRANCE
- 地址: 1. Natl Res Ctr, Hormones Dept, Giza, Egypt 2. Mansoura Univ, Fac Sci, Div Biochem, Mansoura 35516, Egypt 3. Natl Res Ctr, Chem Nat Cpds Dept, Giza, Egypt
- ISBN: 0223-5234
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