Identification and characterization of novel inhibitors of mPTPB, an essential virulent phosphatase from mycobacterium tuberculosis

Lan Chen, Bo Zhou, Sheng Zhang, Li Wu, Yuehong Wang, Scott G. Franzblau, Zhong Yin Zhang

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Mycobacterium protein tyrosine phosphatase B (mPTPB) is an essential virulence factor required for Mycobacterium tuberculosis (Mtb) survival in host macrophages. Consequently, mPTPB represents an exciting new target with a completely novel mechanism of action. We screened a library of 7500 compounds against mPTPB and identified several 2-oxo-1,2-dihydrobenzo[cd]indole-6- sulfonamide and piperazinyl-thiophenyl-ethyl-oxalamide derivatives as two distinct classes of mPTPB inhibitors. We showed that both classes of inhibitors are capable of blocking the mPTPB-mediated ERK1/2 inactivation. We further demonstrated that both classes of mPTPB inhibitors are effective in inhibiting the growth of Mtb in macrophages. Thus, improvement of the lead compounds may produce a novel class of anti-TB agents.

Original languageEnglish (US)
Pages (from-to)355-359
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume1
Issue number7
DOIs
StatePublished - Oct 14 2010

    Fingerprint

Keywords

  • anti-TB agents
  • high throughput screening
  • mPTPB inhibitors
  • Mycobacterium tuberculosis
  • protein tyrosine phosphatase

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

Cite this