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 Citations (Scopus)

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

Fingerprint

Protein Tyrosine Phosphatases
Mycobacterium
Mycobacterium tuberculosis
Phosphoric Monoester Hydrolases
Macrophages
Lead compounds
Sulfonamides
Virulence Factors
Derivatives
Growth

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

Identification and characterization of novel inhibitors of mPTPB, an essential virulent phosphatase from mycobacterium tuberculosis. / Chen, Lan; Zhou, Bo; Zhang, Sheng; Wu, Li; Wang, Yuehong; Franzblau, Scott G.; Zhang, Zhong-Yin.

In: ACS Medicinal Chemistry Letters, Vol. 1, No. 7, 14.10.2010, p. 355-359.

Research output: Contribution to journalArticle

Chen, Lan ; Zhou, Bo ; Zhang, Sheng ; Wu, Li ; Wang, Yuehong ; Franzblau, Scott G. ; Zhang, Zhong-Yin. / Identification and characterization of novel inhibitors of mPTPB, an essential virulent phosphatase from mycobacterium tuberculosis. In: ACS Medicinal Chemistry Letters. 2010 ; Vol. 1, No. 7. pp. 355-359.
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