Synthesis and cytotoxic effect of pregnenolone derivatives with one or two α,β-unsaturated carbonyls and an ester moiety at C-21 or C-3

Four series of pregnenolone derivatives having one or two alpha,beta-unsaturated carbonyls and an ester moiety at C-21 or C-3 were synthetized to compare their cytotoxicity effect. The final compounds were evaluated on three human cancer cell lines: PC-3 (prostate cancer), MCF-7 (breast cancer), SKLU-1 (lung cancer) and a noncancerous cell line HGF (human gingival fibroblast). Two steroids with a 4-fluorinated benzoic acid ester at C-21 were the most active against lung cancer cell line with IC50 of 13.1 +/- 1.2 and 12.8 +/- 0.5 mu M and showed a low percentage of cytotoxicity for noncancerous cells (27.63 +/- 2.3 and 18.39 +/- 1.2% in the screening at 50 mu M).