TB Research

Synthesis and activity of BNF15 against drug-resistant <i>Mycobacterium tuberculosis</i>

Mahmud HA, Seo H, Kim S, Islam MI, Sultana OF, Nam KW, Lee BE, Sadu VS, et al. (10 authors)

Future medicinal chemistry · 2020-12

Abstract

Aim: Tuberculosis is the leading cause of mortality among infectious diseases worldwide. Finding a new competent anti tubercular therapy is essential. Materials & methods: We screened thousands of compounds and evaluated their efficacy against Mycobacterium tuberculosis . Results: Initially, 2-nitronaphtho[2,3-b]benzofuran-6,11-dione was active against M. tuberculosis . Next, among 15 newly synthesized derivatives, BNF15 showed promising effect against all drug-sensitive and drug-resistant M. tuberculosis (MIC: 0.02-0.78 μg/ml). BNF15 effectively killed intracellular M. tuberculosis and nontuberculous mycobacteria. BNF15 exhibited a prolonged post antibiotic effect superior to isoniazid, streptomycin, and ethambutol and synergistic interaction with rifampicin. In acute oral toxicity test, BNF15 did not show toxic effect at a concentration up to 2000 mg/kg. Conclusion: These results highlight the perspective of BNF15 to treat drug-resistant M. tuberculosis .

MeSH terms

  • Animals
  • Mice, Inbred ICR
  • Humans
  • Mice
  • Gram-Negative Bacteria
  • Gram-Positive Bacteria
  • Mycobacterium tuberculosis
  • Fungi
  • Isoniazid
  • Benzofurans
  • Antitubercular Agents
  • Microbial Sensitivity Tests
  • Drug Resistance, Bacterial
  • DNA Replication
  • Structure-Activity Relationship
  • Drug Synergism
  • Female
  • RAW 264.7 Cells