期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 24, 期 17, 页码 4162-4165出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2014.07.051
关键词
Natural product; Antiviral; HCV entry
资金
- Margaret and Herman Sokol Endowment, Montclair State University
- Sokol Institute for Pharmaceutical Life Sciences
- French 'Agence Nationale de Recherche sur le Sida et les hepatites virales' (ANRS)
- BioImaging Center [ANR-10-EQPX-04-01]
Preventing viral entry into cells is a recognized approach for HIV therapy and has attracted attention for use against the hepatitis C virus (HCV). Recent reports described the activity of (-)-epigallocatechin gallate (EGCG) as an inhibitor of HCV entry with modest potency. EGCG is a polyphenolic natural product with a wide range of biological activity and unfavorable pharmaceutical properties. In an attempt to identify more drug-like EGCG derivatives with improved efficacy as HCV entry inhibitors, we initiated structure-activity investigations using semi-synthetic and synthetic EGCG analogs. The data show that there are multiple regions in the EGCG structure that contribute to activity. The gallate ester portion of the molecule appears to be of particular importance as a 3,4-difluoro analog of EGCG enhanced potency. This derivative and other active compounds were shown not to be cytotoxic in Huh-7 cell culture. These data suggest that more potent, non-cytotoxic EGCG analogs can be prepared in an attempt to identify more drug-like candidates to treat HCV infection by this mechanism. (C) 2014 Elsevier Ltd. All rights reserved.
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