Design and synthesis of an activity-based protein profiling probe derived from cinnamic hydroxamic acid

Teng Ai, Li Qiu, Jiashu Xie, Robert J. Geraghty, Liqiang Chen

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

In our continued effort to discover new anti-hepatitis C virus (HCV) agents, we validated the anti-replicon activity of compound 1, a potent and selective anti-HCV hydroxamic acid recently reported by us. Generally favorable physicochemical and in vitro absorption, distribution, metabolism, and excretion (ADME) properties exhibited by 1 made it an ideal parent compound from which activity-based protein profiling (ABPP) probe 3 was designed and synthesized. Evaluation of probe 3 revealed that it possessed necessary anti-HCV activity and selectivity. Therefore, we have successfully obtained compound 3 as a suitable ABPP probe to identify potential molecular targets of compound 1. Probe 3 and its improved analogs are expected to join a growing list of ABPP probes that have made important contributions to not only the studies of biochemical and cellular functions but also discovery of selective inhibitors of protein targets.

Original languageEnglish (US)
Pages (from-to)686-692
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume24
Issue number4
DOIs
StatePublished - 2016

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.

Keywords

  • Activity-based protein profiling
  • Benzothiophene
  • Cinnamic hydroxamic acid
  • Hepatitis C virus (HCV)
  • Histone deacetylase
  • Hydroxamic acid
  • Matrix metalloproteinases

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