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

Rohit Bhat, Amna T. Adam, Jungeun Jasmine Lee, Gaspard Deloison, Yves Rouillé, Karin Séron, David Rotella

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4162-4165
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number17
DOIs
StatePublished - 1 Sep 2014

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Virus Internalization
Viruses
Hepacivirus
Derivatives
Pharmaceutical Preparations
Virus Diseases
Bioactivity
epigallocatechin gallate
Biological Products
Cell culture
Esters
Cell Culture Techniques
HIV
Molecules

Keywords

  • Antiviral
  • HCV entry
  • Natural product

Cite this

Bhat, Rohit ; Adam, Amna T. ; Lee, Jungeun Jasmine ; Deloison, Gaspard ; Rouillé, Yves ; Séron, Karin ; Rotella, David. / Structure-activity studies of (-)-epigallocatechin gallate derivatives as HCV entry inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2014 ; Vol. 24, No. 17. pp. 4162-4165.
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Structure-activity studies of (-)-epigallocatechin gallate derivatives as HCV entry inhibitors. / Bhat, Rohit; Adam, Amna T.; Lee, Jungeun Jasmine; Deloison, Gaspard; Rouillé, Yves; Séron, Karin; Rotella, David.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 24, No. 17, 01.09.2014, p. 4162-4165.

Research output: Contribution to journalArticleResearchpeer-review

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