School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070, PR China.
School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070, PR China.
Bioorg Chem. 2018 Dec;81:107-118. doi: 10.1016/j.bioorg.2018.08.001. Epub 2018 Aug 6.
A series of aryl fluorosulfate analogues (1-37) were synthesized and tested for in vitro antibacterial and antifungal studies, and validated by docking studies. The compounds 9, 12, 14, 19, 25, 26, 35, 36 and 37 exhibited superior antibacterial potency against tested bacterial strains, while compounds 2, 4, 5, 15, 35, 36 and 37 were found to have better antifungal activity against tested fungal strains, compared to standard antibiotic gentamicin and ketoconazole respectively. Among all the synthesized 37 analogs, compounds 25, 26, 35, 36 and 37 displayed excellent anti-biofilm property against Staphylococcus aureus. The structure-activity relationship (SAR) revealed that the antimicrobial activity depends upon the presence of -OSOF group and slender effect of different substituent's on the phenyl rings. The electron donating (OCH) groups in analogs increase the antibacterial activity, and interestingly the electron withdrawing (Cl, NO, F and Br) groups increase the antifungal activity (except compound 35, 36 and 37). The mechanism of potent compounds showed membrane damage on bacteria confirmed by SEM. Compounds 35, 36 and 37 exhibited highest glide g-scores in molecular docking studies and validated the biocidal property.
一系列芳基氟硫酸酯类似物（1-37）被合成并进行了体外抗菌和抗真菌研究，并用对接研究进行了验证。化合物 9、12、14、19、25、26、35、36 和 37 对测试的细菌菌株表现出优异的抗菌效力，而化合物 2、4、5、15、35、36 和 37 与标准抗生素庆大霉素和酮康唑相比，对测试的真菌菌株表现出更好的抗真菌活性。在所合成的 37 种类似物中，化合物 25、26、35、36 和 37 对金黄色葡萄球菌表现出优异的抗生物膜特性。构效关系（SAR）表明，抗菌活性取决于-OSOF 基团的存在以及苯环上不同取代基的细长效应。类似物中供电子（OCH）基团增加了抗菌活性，有趣的是，吸电子（Cl、NO、F 和 Br）基团增加了抗真菌活性（化合物 35、36 和 37 除外）。有力化合物的作用机制通过 SEM 证实了对细菌的膜损伤。化合物 35、36 和 37 在分子对接研究中表现出最高的滑行 g 分数，并验证了杀菌性能。
