title: Structure-activity studies of (-)-epigallocatechin gallate derivatives as HCV entry inhibitors.
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.
authors.affiliation: Department of Chemistry and Biochemistry, Montclair State University, Montclair, NJ 07043, United States.
authors.forename: Rohit
authors.initials: R
authors.lastname: Bhat
authors.affiliation: Department of Chemistry and Biochemistry, Montclair State University, Montclair, NJ 07043, United States.
authors.forename: Amna T
authors.initials: AT
authors.lastname: Adam
authors.affiliation: Department of Chemistry and Biochemistry, Montclair State University, Montclair, NJ 07043, United States.
authors.forename: Jungeun Jasmine
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: BioImaging Center Lille-Nord de France, IFR142, Institut Pasteur de Lille, F-59021 Lille, France.
authors.forename: Gaspard
authors.initials: G
authors.lastname: Deloison
authors.affiliation: 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.
authors.forename: Yves
authors.initials: Y
authors.lastname: Rouillé
authors.affiliation: 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.
authors.forename: Karin
authors.initials: K
authors.lastname: Séron
authors.affiliation: Department of Chemistry and Biochemistry, Montclair State University, Montclair, NJ 07043, United States. Electronic address: rotellad@mail.montclair.edu.
authors.forename: David P
authors.initials: DP
authors.lastname: Rotella
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D002392:Catechin; C045651:epigallocatechin gallate
keywords: Antiviral; HCV entry; Natural product