Synthesis and Evaluation of Acylated Derivatives of Hederagenin as Inhibitors of HIV-1 and HCV NS3/4A Proteases
Synthesis and Evaluation of Acylated Derivatives of Hederagenin as Inhibitors of HIV-1 and HCV NS3/4A Proteases
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DOI：
10.1177/1934578x221075083
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Xia Wang
中科院分区：
文献类型：
--
作者：
Qing Liu;Ying Wei;Yongjia Hao;Jian Yang;Bowen Pan;Xiaosheng Yang;Ying Zhou;Xia Wang
Viral infection imposes a major threat to human health. To develop new potent antiviral agents, Hederagenin (HE), a known inhibitor of HIV-1 and HCV NS3/4A proteases, was used as a starting material to synthesize 4 types of HE derivatives, HE-3,23-diacyl,.HES-3,23-diacyl, HES-3-acyl, and HES-3-oxo-23-acyl. We evaluated the in vitro inhibitory activities of the derivatives against HIV-1.and HCV NS3/4A proteases. (3β,23)-Di-O-diglutaryl-hederagenin (1b) and (3β,23)-di-O-(3′.,3′.-dimethylsuccinyl-hederagenin ethyl.ester (2b) exhibited potent inhibitory activities against the HIV-1 and/or HCV NS3/4A proteases with IC50 values < 10 μM,.but did not appreciably inhibit general human proteases renin and trypsin. The SARs showed that dicarboxylic acid hemiesters.of HE significantly enhance the antiviral activities when C3 or C23 are linked with 6 carbon acyl chains.
