Indole-2-Carboxamides Are Active against Mycobacterium abscessus in a Mouse Model of Acute Infection

Antimicrob Agents Chemother. 2019 Feb 26;63(3):e02245-18. doi: 10.1128/AAC.02245-18. Print 2019 Mar.

Abstract

Nontuberculous mycobacteria (NTM) pathogens particularly infect patients with structural lung disorders. We previously reported novel indole-2-carboxamides (ICs) that are active against a wide panel of NTM pathogens. This study discloses in vivo data for two lead molecules (compounds 5 and 25) that were advanced for efficacy studies in Mycobacterium abscessus-infected mouse models. Oral administration of the lead molecules showed a statistically significant reduction in the bacterial loads in lung and spleen of M. abscessus-infected mice.

Keywords: MmpL3; Mycobacterium; Mycobacterium abscessus; NTM; indole-2-carboxamide; nontuberculous mycobacteria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / therapeutic use*
  • Disease Models, Animal
  • Female
  • Indoles / pharmacokinetics
  • Indoles / therapeutic use*
  • Membrane Transport Proteins / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Microbial Sensitivity Tests
  • Mycobacterium Infections, Nontuberculous / drug therapy*
  • Mycobacterium Infections, Nontuberculous / microbiology
  • Mycobacterium abscessus / drug effects*
  • Mycobacterium abscessus / genetics

Substances

  • Anti-Bacterial Agents
  • Indoles
  • Membrane Transport Proteins