Benzofuroxan Derivatives as Potent Agents against Multidrug-Resistant Mycobacterium tuberculosis

ChemMedChem. 2021 Apr 20;16(8):1268-1282. doi: 10.1002/cmdc.202000899. Epub 2021 Feb 9.

Abstract

Tuberculosis (TB) is currently the leading cause of death related to infectious diseases worldwide, as reported by the World Health Organization. Moreover, the increasing number of multidrug-resistant tuberculosis (MDR-TB) cases has alarmed health agencies, warranting extensive efforts to discover novel drugs that are effective and also safe. In this study, 23 new compounds were synthesized and evaluated in vitro against the drug-resistant strains of M. tuberculosis. The compound 6-((3-fluoro-4-thiomorpholinophenyl)carbamoyl)benzo[c][1,2,5]oxadiazole 1-N-oxide (5 b) was particularly remarkable in this regard as it demonstrated MIC90 values below 0.28 μM against all the MDR strains evaluated, thus suggesting that this compound might have a different mechanism of action. Benzofuroxans are an attractive new class of anti-TB agents, exemplified by compound 5 b, with excellent potency against the replicating and drug-resistant strains of M. tuberculosis.

Keywords: N-oxide; antitubercular agents; benzofuroxan; multidrug-resistant TB; tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / pharmacology*
  • Benzoxazoles / chemical synthesis
  • Benzoxazoles / pharmacology*
  • Drug Design
  • Drug Resistance, Multiple / drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antitubercular Agents
  • Benzoxazoles
  • Oxadiazoles
  • benzofuroxan