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