The abyssomicin C family as in vitro inhibitors of Mycobacterium tuberculosis

Tuberculosis (Edinb). 2010 Sep;90(5):298-300. doi: 10.1016/j.tube.2010.08.002. Epub 2010 Aug 23.

Abstract

The antimycobacterial efficacy of the abyssomicin C family of natural products, in addition to a key synthetic intermediate, has been investigated given their reported inhibition of Bacillus subtilis p-aminobenzoate biosynthesis. The naturally occurring (-)-abyssomicin C and its atropisomer were found to exhibit low micromolar growth inhibition against the relatively fast-growing and non-virulent Mycobacterium smegmatis and the vaccine strain Mycobacterium bovis BCG, while their antipodes were slightly less active. (-)-abyssomicin C and its atropisomer were particularly efficacious against Mycobacterium tuberculosis H37Rv, exhibiting MIC values of 3.6 and 7.2 μM, respectively. More specifically, (-)-abyssomicin C was bactericidal. This complex natural product and its analogs, thus, hold promise as chemical tools in the study of M. tuberculosis metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminobenzoic Acid / metabolism
  • Antitubercular Agents / metabolism
  • Antitubercular Agents / pharmacology*
  • Bacillus subtilis / drug effects
  • Bacillus subtilis / metabolism
  • Bridged Bicyclo Compounds, Heterocyclic / metabolism
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Humans
  • Isomerism
  • Microbial Sensitivity Tests
  • Mycobacterium bovis / drug effects
  • Mycobacterium smegmatis / drug effects
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / metabolism

Substances

  • Antitubercular Agents
  • Bridged Bicyclo Compounds, Heterocyclic
  • abyssomicin C
  • 4-Aminobenzoic Acid