Synthesis and biological activity of alkynoic acids derivatives against mycobacteria

Catherine Vilchèze, Lawrence W. Leung, Robert Bittman, William R. Jacobs

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

2-Alkynoic acids have bactericidal activity against Mycobacterium smegmatis but their activity fall sharply as the length of the carbon chain increased. In this study, derivatives of 2-alkynoic acids were synthesized and tested against fast- and slow-growing mycobacteria. Their activity was first evaluated in M. smegmatis against their parental 2-alkynoic acids, as well as isoniazid, a first-line antituberculosis drug. The introduction of additional unsaturation or heteroatoms into the carbon chain enhanced the antimycobacterial activity of longer chain alkynoic acids (more than 19 carbons long). In contrast, although the modification of the carboxylic group did not improve the antimycobacterial activity, it significantly reduced the toxicity of the compounds against eukaryotic cells. Importantly, 4-(alkylthio)but-2-ynoic acids, had better bactericidal activity than the parental 2-alkynoic acids and on a par with isoniazid against the slow-grower Mycobacterium bovis BCG. These compounds had also low toxicity against eukaryotic cells, suggesting that they could be potential therapeutic agents against other types of topical mycobacterial infections causing skin diseases including Mycobacterium abscessus, Mycobacterium ulcerans, and Mycobacterium leprae. Moreover, they provide a possible scaffold for future drug development.

Original languageEnglish (US)
Pages (from-to)125-138
Number of pages14
JournalChemistry and Physics of Lipids
Volume194
DOIs
StatePublished - Jan 1 2016

Fingerprint

Mycobacterium
Bioactivity
Derivatives
Acids
Mycobacterium smegmatis
Carbon
Isoniazid
Eukaryotic Cells
Mycobacterium bovis
Toxicity
Mycobacterium ulcerans
Mycobacterium leprae
Skin Diseases
Scaffolds
Pharmaceutical Preparations
Skin
Infection

Keywords

  • Alkynoic
  • Antimycobacterial
  • InhA
  • Sulfur

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Cell Biology

Cite this

Synthesis and biological activity of alkynoic acids derivatives against mycobacteria. / Vilchèze, Catherine; Leung, Lawrence W.; Bittman, Robert; Jacobs, William R.

In: Chemistry and Physics of Lipids, Vol. 194, 01.01.2016, p. 125-138.

Research output: Contribution to journalArticle

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