Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, Hradec Králové, 500 05, Czech Republic.
Med Chem. 2012 Mar;8(2):281-92. doi: 10.2174/157340612800493593.
A set of 2-benzylsulfanyl derivatives of benzothiazole was synthesized and evaluated for antimicrobial and cytotoxic activities. The biological screening on antimicrobial activity against a panel of Gram-positive and Gram-negative bacteria, yeasts and fungi identified benzylsulfanyl derivatives of benzothiazole as selective inhibitors of mycobacteria. The lead compounds in the set, dinitro derivatives exhibited significant activity against sensitive and multidrug-resistant strains of M. tuberculosis and low cytotoxicity. The QSAR study indicated that the antituberculotic activity is connected with LUMO and HOMO energies. The lower lipophilicity and the increased size of the molecule contribute to antituberculotic activity. Thus, dinitrobenzylsulfanyl derivatives of benzothiazole represent promising smallmolecule synthetic antimycobacterials.
一组 2-苄基硫基苯并噻唑衍生物被合成并评估了它们的抗菌和细胞毒性活性。对一组革兰氏阳性和革兰氏阴性细菌、酵母和真菌的抗菌活性进行生物筛选，鉴定出苯并噻唑的苄基硫基衍生物是分枝杆菌的选择性抑制剂。该系列中的先导化合物二硝基衍生物对敏感和耐多药结核分枝杆菌菌株表现出显著的活性和低细胞毒性。QSAR 研究表明，抗结核活性与 LUMO 和 HOMO 能量有关。较低的亲脂性和分子尺寸的增加有助于抗结核活性。因此，二硝基苄基硫基苯并噻唑衍生物代表了有前途的小分子合成抗分枝杆菌药物。
