Synthesis And Activity Of Bnf15 Against Drug-Resistant Mycobacterium Tuberculosis

FUTURE MEDICINAL CHEMISTRY(2021)

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摘要
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 x15 newly synthesized derivatives, BNF15 showed promising effect against all drug-sensitive and drug-resistant M. tuberculosis (MIC: 0.02-0.78 mu g/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.
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关键词
acute oral toxicity, BNF15, drug-resistant M, tuberculosis, drug combination, PAE
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