Synthesis and cytotoxic evaluation of four new 6E-hydroximinosteroids

Abstract

Four new 6E-hydroximinosteroids (1, 2a, 3 and 4) have been synthesized from the corresponding ketones, 2β,3β-dihydroxy-5α-cholestan-6-one (5), 2α,3α-dihydroxy-5α-cholestan-6-one (6), 2β,3α-dihydroxy-5α-cholestan-6-one (7) and 2β,3α-dihydroxy-5α-cholestan-6-one-disulfate (8). The cytotoxic activity of the steroidal oximes was evaluated against two prostate carcinoma cell lines (PC-3 and LNCaP) and compared with that of five polyhydroxylated sulfated analogs (8-12). Oxime 3 and trisulfated analog 11 were the most active compounds with IC50 values of 10.8μM (PC-3) and 7.9μM (LNCaP), respectively.