Synthesis and Evaluation of Acylated Derivatives of Hederagenin as Inhibitors of HIV-1 and HCV NS3/4A Proteases

Viral infection imposes a major threat to human health. To develop new potent antiviral agents, Hederagenin (HE), known inhibitor of HIV-1 and HCV NS3/4A proteases, was used as starting material synthesize 4 types HE derivatives, HE-3,23-diacyl, HES-3,23-diacyl, HES-3-acyl, HES-3-oxo-23-acyl. We evaluated the in vitro inhibitory activities derivatives against proteases. (3 β,23)-Di- O-diglutaryl-hederagenin (1b) β,23)-di- O-(3′,3′-dimethylsuccinyl-hederagenin ethyl ester (2b) exhibited and/or proteases with IC 50 values < 10 μM, but did not appreciably inhibit general renin trypsin. The SARs showed that dicarboxylic acid hemiesters significantly enhance when C3 or C23 are linked 6 carbon acyl chains.