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

Abstract

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 17beta-hydroxy-5alpha-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, 12b, 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 72h, in olive oil, compound 7a was the most effective cytotoxic compound with IC(50) of 30 microM, while the effects of compounds 18 and 23 were approximately similar with IC(50) of 37 microM and 35 microM respectively. While the tested compounds when dissolved in DMSO showed approximately the same IC(50) at both 48 and 72h incubation period, compound 23 was the most effective cytotoxic with IC(50) 42 microM at 48h and 40 microM at 72h. The results of the in vivo study showed that all the tested novel compounds at 25mg/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.

• Authors: Mohamed El-Far, Gamal A Elmegeed, Emad F Eskander, Hanaa M Rady, Mohamed A Tantawy
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 44 Issue 10 Pg. 3936-46 (Oct 2009) ISSN: 1768-3254 [Electronic] France
• PMID: 19447526 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Dihydrotestosterone

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, therapeutic use, toxicity)
• Body Weight (drug effects)
• Carcinoma, Ehrlich Tumor (drug therapy)
• Carcinoma, Hepatocellular (drug therapy)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dihydrotestosterone (analogs & derivatives, chemical synthesis, therapeutic use, toxicity)
• Drug Screening Assays, Antitumor
• Female
• Hematologic Tests
• Humans
• Inhibitory Concentration 50
• Liver Neoplasms (drug therapy)
• Mice
• Structure-Activity Relationship