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

Authors :: Du NN
Li X
Wang YP
Liu F
Liu YX
Li CX
Peng ZG
Gao LM
Jiang JD
Song DQ
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2011 Aug 15; Vol. 21 (16), pp. 4732-5. Date of Electronic Publication: 2011 Jun 23.
Publication Year :: 2011
Abstract: 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.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Subjects :: Anti-Bacterial Agents chemical synthesis
Anti-Bacterial Agents chemistry
Butyrates chemical synthesis
Butyrates chemistry
Down-Regulation drug effects
HSC70 Heat-Shock Proteins metabolism
Hepacivirus drug effects
Hepatitis B virus drug effects
Molecular Conformation
Quinolizines chemical synthesis
Quinolizines chemistry
RNA, Messenger drug effects
Stereoisomerism
Structure-Activity Relationship
Anti-Bacterial Agents pharmacology
Butyrates pharmacology
HSC70 Heat-Shock Proteins antagonists & inhibitors
Quinolizines pharmacology

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