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

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 17β-hydroxy-5α-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 72 h, in olive oil, compound 7a was the most effective cytotoxic compound with IC50 of 30 μM, while the effects of compounds 18 and 23 were approximately similar with IC50 of 37 μM and 35 μM 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 μM at 48 h and 40 μM 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.

Several thiazolo, pyrido, pyrano and lactam steroid derivatives were obtained using 17β-hydroxy-5α-androstan-3-one 1 as starting steroid. All tested compounds gave the best results when dissolved in olive oil in 50 and 100 μM/ml and incubation time 72 h. Aminopyranoandrostane derivative 7a was the most effective among the other tested compounds (IC50 = 30 μM), while the effects of compounds 18 and 23 were approximately similar (IC50 = 37 μM and 35 μM respectively). In the case of using DMSO as solvent, IC50 of all tested compounds elevated than that obtained in the case of olive oil. However, aza-A-homoandrostan-3-one 23 showed good inhibition of HepG2 cells when dissolved in DMSO in 50 and 100 μM/ml at incubation time 72 h (IC50 = 40 μM). The results revealed that olive oil is the suitable vehicle for anti-tumor drugs and is better than DMSO in this respect.Figure optionsDownload as PowerPoint slide