Synthesis, biological evaluation, and structure-activity relationships for 5-[(E)-2-arylethenyl]-3-isoxazolecarboxylic acid alkyl ester derivatives as valuable antitubercular chemotypes

Marco Pieroni, Annamaria Lilienkampf, Wan Baojie, Wang Yuehong, Scott G. Franzblau, Alan P. Kozikowski

Research output: Contribution to journalArticle

Abstract

Tuberculosis (TB), mostly caused by Mycobacterium tuberculosis (Mtb), is one of the leading causes of death from infectious disease worldwide. Its coinfection with HIV and the emergence of multidrugresistant TB(MDR-TB) and extensively drug-resistant TB (XDR-TB) strains have further worsened the TB pandemic. Despite its global impact, TB is considered a neglected disease and no new anti-TB therapeutics have been introduced over the last four decades. The nonreplicating persistent form of TB (NRP-TB) is responsible for the length of the treatment and is the putative cause of treatment failure. Therefore, new anti-TB agents, which are active against both the replicating form of Mtb (R-TB) and NRP-TB, are urgently needed. Herein, we report the synthesis and structure-activity relationships (SAR) of a series of 5-[(E)-2-arylethenyl]-3- isoxazolecarboxylic acid alkyl esters as potent anti-TB agents. Several compounds had submicromolar minimum inhibitory concentrations (MIC) against R-TB and were active against NRP-TB in the low micromolar range, thus representing attractive lead compounds for the possible development of new anti-TB agents.

Original languageEnglish (US)
Pages (from-to)6287-6296
Number of pages10
JournalJournal of Medicinal Chemistry
Volume52
Issue number20
DOIs
StatePublished - Oct 22 2009
Externally publishedYes

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Structure-Activity Relationship
Esters
Tuberculosis
Acids
Mycobacterium tuberculosis
Extensively Drug-Resistant Tuberculosis
Neglected Diseases
Microbial Sensitivity Tests
Pandemics
Treatment Failure
Coinfection
Communicable Diseases
Cause of Death
HIV

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Synthesis, biological evaluation, and structure-activity relationships for 5-[(E)-2-arylethenyl]-3-isoxazolecarboxylic acid alkyl ester derivatives as valuable antitubercular chemotypes. / Pieroni, Marco; Lilienkampf, Annamaria; Baojie, Wan; Yuehong, Wang; Franzblau, Scott G.; Kozikowski, Alan P.

In: Journal of Medicinal Chemistry, Vol. 52, No. 20, 22.10.2009, p. 6287-6296.

Research output: Contribution to journalArticle

Pieroni, Marco ; Lilienkampf, Annamaria ; Baojie, Wan ; Yuehong, Wang ; Franzblau, Scott G. ; Kozikowski, Alan P. / Synthesis, biological evaluation, and structure-activity relationships for 5-[(E)-2-arylethenyl]-3-isoxazolecarboxylic acid alkyl ester derivatives as valuable antitubercular chemotypes. In: Journal of Medicinal Chemistry. 2009 ; Vol. 52, No. 20. pp. 6287-6296.
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