Synthesis, structure−activity relationship and biological evaluation of novel N-substituted matrinic acid derivatives as host heat-stress cognate 70 (Hsc70) down-regulators

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• 作者：Na-Na Du^† ; ; ^a ; Xin Li^† ; ; ^a ; Yu-Ping Wang^a ; Fei Liu^a ; Yan-Xin Liu^a ; Chun-Xin Li^a ; Zong-Gen Peng^a ; Li-Mei Gao^a ; Jian-Dong Jiang ; ^a ; ^{jiang.jdong@163.com"" rel=""nofollow} ; Dan-Qing Song ; ^a ; ^{songdanqingsdq@hotmail.com"" rel=""nofollow}
• 关键词：N-Substituted matrinic acid ; Heat-stress cognate 70 (Hsc70) ; Structure– ; activity relationship ; Mechanism ; Down-regulators ; Anti-HBV activity
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：15 August 2011
• 年：2011
• 卷：21
• 期：16
• 页码：4732-4735
• 全文大小：425 K

文摘

Oxymatrine (1) is a natural anti-hepatitis B virus (HBV) drug that down-regulates host heat-stress cognate 70 (Hsc70) expression through a mechanism different from that of nucleosides. Taking Hsc70 as a target against HBV, 26 novel N-substituted matrinic acid analogs were designed, synthesized and evaluated for their regulation of Hsc70 mRNA expression with 1 as the lead. The SAR analysis revealed that (i) the carboxyl group at the 11-position was required for activity; (ii) introducing of a substituent on the nitrogen atom at the 12-position of 3, especially substituted benzyl, might significantly improve the activity. Among these analogs, compound 9p possessing N-p-methoxylbenzyl afforded an increased anti-HBV effect in comparison with 1. We consider 9p a promising anti-HBV candidate.