2. Academic Validation
  3. Structure-activity studies of (-)-epigallocatechin gallate derivatives as HCV entry inhibitors

Structure-activity studies of (-)-epigallocatechin gallate derivatives as HCV entry inhibitors

  • Bioorg Med Chem Lett. 2014 Sep 1;24(17):4162-5. doi: 10.1016/j.bmcl.2014.07.051.
Rohit Bhat 1,  Amna T Adam 1,  Jungeun Jasmine Lee 1,  Gaspard Deloison 2,  Yves Rouillé 3,  Karin Séron 4,  David P Rotella 5
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, Montclair State University, Montclair, NJ 07043, United States.
  • 2 BioImaging Center Lille-Nord de France, IFR142, Institut Pasteur de Lille, F-59021 Lille, France.
  • 3 Hepatitis C Laboratory, Center for Infection & Immunity of Lille (CIIL), Université Lille Nord de France, Institut Pasteur de Lille, CNRS-UMR8204, Inserm-U1019, F-59021 Lille, France.
  • 4 Hepatitis C Laboratory, Center for Infection & Immunity of Lille (CIIL), Université Lille Nord de France, Institut Pasteur de Lille, CNRS-UMR8204, Inserm-U1019, F-59021 Lille, France. Electronic address: karin.seron@ibl.cnrs.fr.
  • 5 Department of Chemistry and Biochemistry, Montclair State University, Montclair, NJ 07043, United States. Electronic address: rotellad@mail.montclair.edu.
PMID: 25103601 DOI: 10.1016/j.bmcl.2014.07.051
Abstract

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.

Keywords

Antiviral; HCV entry; Natural product.

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