School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara Jaú Highway KM 01, 14800903, Araraquara, Brazil.
Institute of Chemistry, São Paulo State University (UNESP), Francisco Degni Street 55, 14800060, Araraquara, Brazil.
ChemMedChem. 2021 Apr 20;16(8):1268-1282. doi: 10.1002/cmdc.202000899. Epub 2021 Feb 9.
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 MIC 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.
据世界卫生组织报告，结核病（TB）目前是全球与传染病相关的主要死亡原因。此外，越来越多的耐多药结核病（MDR-TB）病例引起了卫生机构的警觉，需要大力寻找有效且安全的新型药物。在这项研究中，合成了 23 种新化合物，并在体外对耐多药结核分枝杆菌菌株进行了评估。化合物 6-((3-氟-4-硫代吗啉基)氨基甲酰)苯并[c][1,2,5]恶二唑 1-N-氧化物（5b）在这方面表现尤为突出，因为它对所有评估的 MDR 菌株的 MIC 值均低于 0.28 μM，这表明该化合物可能具有不同的作用机制。苯并呋咱类是一类有吸引力的新型抗结核药物，以化合物 5b 为代表，对结核分枝杆菌的复制和耐药菌株具有极好的活性。
