Department of Polymer Engineering, Faculty of Technology, Karabuk University, 78050, Karabuk, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Biruni University, 34010, Istanbul, Turkey.
Mol Inform. 2018 Mar;37(3). doi: 10.1002/minf.201700083. Epub 2017 Sep 6.
In this study, a novel series of phenyl substituted imidazo[2,1-b][1,3,4]thiadiazole derivatives were synthesized, characterized and explored for antibacterial activity against Gram-negative Escherichia coli, Gram-positive Staphylococcus aureus and Bacillus subtilis and antifungal activity against Candida albicans. Most of the synthesized compounds exhibited remarkable antimicrobial activities, some of which being ten times more potent than positive controls. The most promising compound showed excellent activity with MIC value of 0.03 μg/ml against both S. aureus and B. subtilis (MIC values of positive compound Chloramphenicol are 0.4 μg/ml and 0.85 μg/ml, respectively). Furthermore, structure-activity relationship was also investigated with the help of computational tools. Some physicochemical and ADME properties of the compounds were calculated too. The combination of electronic structure calculations performed at PM6 level and molecular docking simulations using Glide extra-precision mode showed that the hydrophobic nature of keto aryl ring with no electron withdrawing substituents at para position enhances activity while electron-donating substituents at the second aryl ring is detrimental to activity.
在这项研究中，我们合成了一系列新型的苯基取代的咪唑并[2,1-b][1,3,4]噻二唑衍生物，并对其进行了表征，同时还研究了它们对革兰氏阴性大肠杆菌、革兰氏阳性金黄色葡萄球菌和枯草芽孢杆菌的抗菌活性以及对白色念珠菌的抗真菌活性。大多数合成的化合物表现出显著的抗菌活性，其中一些化合物的活性比阳性对照物强十倍。最有前途的化合物对金黄色葡萄球菌和枯草芽孢杆菌均表现出优异的活性，其 MIC 值分别为 0.03μg/ml（阳性对照物氯霉素的 MIC 值分别为 0.4μg/ml 和 0.85μg/ml）。此外，还借助计算工具研究了构效关系。还计算了化合物的一些物理化学和 ADME 性质。在 PM6 水平上进行的电子结构计算与使用 Glide 超高精度模式进行的分子对接模拟相结合表明，具有无吸电子取代基的酮芳环的疏水性以及在第二芳环上具有供电子取代基不利于活性。
