The burden of antibiotic resistance necessitates a continued search for new antimicrobials. We evaluated the antimicrobial activities of novel benzothiazoles synthesized by our group. Antibacterial activity was evaluated in vitro in Staphylococcus aureus, Bacillus subtilis, and Escherichia coli, while the antifungal activity was tested in Candida albicans and Aspergillus niger, and expressed as the minimum inhibitory concentration (MIC; µg/mL). MIC values of benzothiazole compounds ranged from 25 to 200 µg/mL. Compounds 3 and 4 gave high antibacterial and moderate antifungal activities, while 10 and 12 showed moderate activity against all tested organisms. In addition, some benzothiazole compounds significantly suppressed the activity of Escherichia coli dihydroorotase and inhibited the dimorphic transition of Candida albicans. Moreover, the active benzothiazole compounds induced DNA and protein leakage in Aspergillus niger spores. Molecular interactions of benzothiazole derivatives with dihydroorotase revealed the formation of hydrogen bonds with the active site residues LEU222 or ASN44. Strong hydrophobic interactions of the bulky thiazole and naphthalene rings at the entrance to the active site might interfere with the access of substrates to their binding sites, which results in dihydroorotase inhibition. Thus, inhibition of dihydroorotase might contribute to the observed antimicrobial actions of these compounds.

中文翻译：

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新型苯并噻唑衍生物作为潜在抗菌剂的筛选和分子对接。

抗生素抗性的负担使得必须继续寻找新的抗菌剂。我们评估了由我们小组合成的新型苯并噻唑的抗菌活性。在体外评估了金黄色葡萄球菌，枯草芽孢杆菌和大肠杆菌的抗菌活性，而在白色念珠菌和黑曲霉中测试了抗菌活性，并以最小抑制浓度（MIC; µg / mL）表示。苯并噻唑化合物的MIC值为25至200 µg / mL。化合物3和4具有较高的抗菌和中等的抗真菌活性，而化合物10和12对所有受测生物均具有中等的活性。另外，一些苯并噻唑化合物显着抑制了大肠杆菌二氢乳清酶的活性，并抑制了白色念珠菌的二态转变。此外，活性苯并噻唑化合物诱导黑曲霉孢子DNA和蛋白质泄漏。苯并噻唑衍生物与二氢乳清酶的分子相互作用揭示了与活性位点残基LEU222或ASN44形成氢键。活性位点入口处大的噻唑和萘环的强疏水相互作用可能会干扰底物接近其结合位点，从而导致二氢乳清酶的抑制。因此，抑制二氢乳清酶可能有助于观察到的这些化合物的抗菌作用。活性位点入口处大的噻唑和萘环的强疏水相互作用可能会干扰底物接近其结合位点，从而导致二氢乳清酶的抑制。因此，抑制二氢乳清酶可能有助于观察到的这些化合物的抗菌作用。活性位点入口处大的噻唑和萘环的强疏水相互作用可能会干扰底物接近其结合位点，从而导致二氢乳清酶的抑制。因此，抑制二氢乳清酶可能有助于观察到的这些化合物的抗菌作用。