title: Hydroxamic acids block replication of hepatitis C virus.
abstract: Intrigued by the role of protein acetylation in hepatitis C virus (HCV) replication, we tested known histone deacetylase (HDAC) inhibitors and a focused library of structurally simple hydroxamic acids for inhibition of a HCV subgenomic replicon. While known HDAC inhibitors with varied inhibitory profiles proved to be either relatively toxic or ineffective, structure-activity relationship (SAR) studies on cinnamic hydroxamic acid and benzo[b]thiophen-2-hydroxamic acid gave rise to compounds 22 and 53, which showed potent and selective anti-HCV activity and therefore are promising starting points for further structural optimization and mechanistic studies.
authors.affiliation: Center for Drug Design, Academic Health Center, University of Minnesota , 516 Delaware Street S.E., Minneapolis, Minnesota 55455, United States.
authors.forename: Teng
authors.initials: T
authors.lastname: Ai
authors.forename: Yanli
authors.initials: Y
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Qiu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Geraghty
authors.forename: Liqiang
authors.initials: L
authors.lastname: Chen
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids