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

被引：65

作者：

Du, Na-Na

Li, Xin

Wang, Yu-Ping

Liu, Fei

Liu, Yan-Xin

Li, Chun-Xin

Peng, Zong-Gen

Gao, Li-Mei

Jiang, Jian-Dong ^{[1
]}

Song, Dan-Qing

机构：

[1] Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 16期

关键词：

N-Substituted matrinic acid; Heat-stress cognate 70 (Hsc70); Structure-activity relationship; Mechanism; Down-regulators; Anti-HBV activity; CHRONIC HEPATITIS-B; VIRUS; REPLICATION; ALKALOIDS; PROTEIN;

D O I：

10.1016/j.bmcl.2011.06.071

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

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. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：4732 / 4735

页数：4

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