Design, synthesis and biological evaluation of novel α-hederagenin derivatives with anticancer activity

In an attempt to arrive at a more potent cytotoxic agent than the parent compound a-hederagenin (H), 24 alpha-hederagenin derivatives (5-8,11-24, 27-28, 31-32, and 35-36) were synthesized in a concise and efficient strategy and screened for in vitro cytotoxicity against the human cancer cell lines MKN45 and KB. Among these compounds, the polyamine derivative 15 exhibited more potency than the parent compound with IC50 values in the range of 4.22 AM-8.05 mu M. Compound 15 increased Baxibc1-2 ratio that disrupted the mitochondrial potential and induced apoptosis. Therefore, the present studies highlight the importance of polyamine derivatives of alpha-hederagenin in the discovery and development of novel anticancer agents. (C) 2017 Elsevier Masson SAS. All rights reserved.