Design, synthesis and antiproliferative evaluation of some B-homo steroidal lactams

Abstract

A series of 3-substituted-6-aza-B-homo-5-α-stigmastan-7-one and 3-substituted-6-aza-B-homo-5-α-sitostan-7-one derivatives were designed and synthesized by the oxidation, reduction, oximation, Beckman rearrangement and condensation reaction. Their structures were characterized. The antiproliferative activities were assayed, and some of the compounds synthesized displayed distinct cytotoxicity against SGC 7901, CNE, HeLa and Bel 7404 cancer cells. Our results revealed that the compounds with the side chain of sitosterol had better antiproliferative activity than the compounds with the side chain of stigmasterol. The compound 11b with 3-thiosemicarbazone and 12b with 3-(4′-methyl)thiosemicarbazone group displayed an excellent antiproliferative activity against Bel-7404 cells owning an IC50 value of 3.9 and 5.6 μM, respectively (compared with cisplatin, IC50: 11.6 μM). The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.