Synthesis and activity of BNF15 against drug-resistant Mycobacterium tuberculosis.


Mahmud HA(1), Seo H(1), Kim S(1), Islam MI(1), Sultana OF(1), Nam KW(2), Lee BE(3), Sadu VS(4), Lee KI(4)(5), Song HY(1).
Author information:
(1)Department of Microbiology & Immunology, School of Medicine, Soonchunhyang University, Cheonan, Chungnam 31151, South Korea.
(2)Department of Life Science & Biotechnology, Soonchunhyang University, Asan, Chungnam 31538, South Korea.
(3)Department of Chemistry, School of Life Sciences, Soonchunhyang University, Asan, Chungnam 31538, South Korea.
(4)Major of Green Chemistry & Environmental Biotechnology, University of Science & Technology, Daejeon 34113, South Korea.
(5)Green Chemistry Division, Korea Research Institute of Chemical Technology, Daejeon 34114, South Korea.


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.