Synthesis and antitumor activity of novel steroidal imidazolium salt derivatives

Sixty-one novel steroidal imidazolium salt derivatives were synthesized and evaluated in vitro against a panel of human tumor cell lines. The results showed that diosgenin-imidazolium salt derivatives displayed much higher cytotoxic activities than cholesterol-imidazolium salts and dehydroepiandrosterone-imidazolium salts. The SARs results suggested that the existence of substituted 5,6-dimethyl-benzimidazoles or benzimidazole ring and substitution of the imidazolyl-3 alpha-position with a 2-bromobenzyl or 2-naphthylmethyl group could be critical for promoting cytotoxic activity. Diosgenin-imidazolium salt a30 was found to be the most potent compound with IC(50 )values of 0.44-0.79 mu M against five human tumor cell lines. Compound a24 showed inhibitory activity selectively against SMMC7721 cell lines with IC50 value of 0.21 mu M and 54-fold more sensitive to DDP. Moreover, compound a30 inhibited cell proliferation through inducing the G0/G1 cell cycle arrest and apoptosis in SMMC-7721 cells. (C) 2019 Elsevier Masson SAS. All rights reserved.