Hydroxamic acids block replication of hepatitis c virus

Teng Ai; Yanli Xu; Li Qiu; Robert J. Geraghty; Liqiang Chen

doi:10.1021/jm501330g

Hydroxamic acids block replication of hepatitis c virus

Teng Ai, Yanli Xu, Li Qiu, Robert J. Geraghty, Liqiang Chen

Center for Drug Design

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

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.

Original language	English (US)
Pages (from-to)	785-800
Number of pages	16
Journal	Journal of medicinal chemistry
Volume	58
Issue number	2
DOIs	https://doi.org/10.1021/jm501330g
State	Published - Jan 22 2015

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Publisher Copyright:
© 2014 American Chemical Society.

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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.",

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AU - Xu, Yanli

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AU - Geraghty, Robert J.

AU - Chen, Liqiang

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AB - 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.

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Hydroxamic acids block replication of hepatitis c virus

Abstract

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