Characterization of Two Novel Inhibitors of the Mycobacterium tuberculosis Cytochrome bc1 Complex

Antimicrob Agents Chemother. 2023 Jul 18;67(7):e0025123. doi: 10.1128/aac.00251-23. Epub 2023 Jun 26.

Abstract

Drug-resistant tuberculosis is a global health care threat calling for novel effective treatment options. Here, we report on two novel cytochrome bc1 inhibitors (MJ-22 and B6) targeting the Mycobacterium tuberculosis respiratory chain with excellent intracellular activities in human macrophages. Both hit compounds revealed very low mutation frequencies and distinct cross-resistance patterns with other advanced cytochrome bc1 inhibitors.

Keywords: ATP; Mycobacterium tuberculosis; QcrB; antibiotic; cytochrome bc1; drug screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology
  • Cytochromes / pharmacology
  • Electron Transport
  • Electron Transport Complex III / genetics
  • Humans
  • Mycobacterium tuberculosis* / genetics
  • Tuberculosis, Multidrug-Resistant*

Substances

  • Antitubercular Agents
  • Cytochromes
  • Electron Transport Complex III