Rationally designed nucleoside antibiotics that inhibit siderophore biosynthesis of Mycobacterium tuberculosis

J Med Chem. 2006 Jan 12;49(1):31-4. doi: 10.1021/jm051060o.

Abstract

A rationally designed nucleoside inhibitor of Mycobacterium tuberculosis growth (MIC(99) = 0.19 microM) that disrupts siderophore biosynthesis was identified. The activity is due to inhibition of the adenylate-forming enzyme MbtA which is involved in biosynthesis of the mycobactins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antitubercular / chemical synthesis
  • Antibiotics, Antitubercular / chemistry
  • Antibiotics, Antitubercular / pharmacology*
  • Crystallography, X-Ray
  • Drug Design
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Nucleosides / chemical synthesis
  • Nucleosides / chemistry
  • Nucleosides / pharmacology*
  • Siderophores / antagonists & inhibitors*
  • Siderophores / biosynthesis
  • Structure-Activity Relationship

Substances

  • Antibiotics, Antitubercular
  • Nucleosides
  • Siderophores