A new class of salicylic acid derivatives for inhibiting YopH of Yersinia pestis

Mahesh P. Paudyal, Li Wu, Zhong Yin Zhang, Christopher D. Spilling, Chung F. Wong

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Previously, we identified a class of salicylic acid derivatives that display inhibitory activity against the protein tyrosine phosphatase YopH from Yersinia pestis. Because docking study suggested that the large phenyl ring attaching to the salicylic acid core might be exposed to the solvent and might not contribute significantly to binding, we have developed a new class of compounds that no longer contain this phenyl ring. We first devised a synthetic scheme for the compounds and then developed an automated computational screening model surrounding this synthetic scheme to help select a small number of compounds for synthesis and experimental testing. Based on this computational screening model and the analysis of the structure-activity relationship of our previous class of compounds, we have synthesized eight compounds and found five that yield micromolar activity. When applying in a larger scale, the synthetic scheme and the computational screening model developed here should help to identify even more potent inhibitors in the future.

Original languageEnglish (US)
Pages (from-to)6781-6788
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number24
DOIs
StatePublished - Dec 15 2014

Keywords

  • Anti-plague agents
  • Biodefense
  • Molecular docking
  • Virtual screening
  • YopH inhibitors

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Medicine(all)

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