Morsy Mohamed A, Ali Enas M, Kandeel Mahmoud, Venugopala Katharigatta N, Nair Anroop B, Greish Khaled, El-Daly Mahmoud
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt.
Antibiotics (Basel). 2020 Apr 29;9(5):221. doi: 10.3390/antibiotics9050221.
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 , , and , while the antifungal activity was tested in and , 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 dihydroorotase and inhibited the dimorphic transition of . Moreover, the active benzothiazole compounds induced DNA and protein leakage in 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.
抗生素耐药性的负担使得人们有必要继续寻找新的抗菌药物。我们评估了本课题组合成的新型苯并噻唑的抗菌活性。在大肠杆菌、金黄色葡萄球菌和粪肠球菌中对其抗菌活性进行了体外评估，而在白色念珠菌和新型隐球菌中测试了其抗真菌活性，并以最低抑菌浓度（MIC；μg/mL）表示。苯并噻唑化合物的MIC值范围为25至200μg/mL。化合物3和4具有较高的抗菌活性和中等的抗真菌活性，而化合物10和12对所有测试微生物均表现出中等活性。此外，一些苯并噻唑化合物显著抑制二氢乳清酸酶的活性并抑制新型隐球菌的二态转变。此外，活性苯并噻唑化合物诱导新型隐球菌孢子中的DNA和蛋白质泄漏。苯并噻唑衍生物与二氢乳清酸酶的分子相互作用揭示了其与活性位点残基LEU222或ASN44形成氢键。在活性位点入口处，庞大的噻唑和萘环的强疏水相互作用可能会干扰底物进入其结合位点，从而导致二氢乳清酸酶受到抑制。因此，抑制二氢乳清酸酶可能有助于这些化合物所观察到的抗菌作用。
