3-S-(β-D-吡喃葡萄糖基)-1,2,4-三唑的合成及抗菌活性

以自制的5-取代芳基-4-氨基-3-巯基-1,2,4三唑为底物, 经糖基修饰后, 在甲醇钠/甲醇/二氯甲烷体系中经水解脱除糖环上的乙酰基, 得到9个新化合物5-取代苯基-4-氨基-3-S-(β-D-吡喃葡萄糖基)-1,2,4-三唑(6a~6i), 其结构经核磁共振波谱(¹H NMR, ¹³C NMR), 红外光谱(IR)和高分辨质谱(HRMS)确认. 生物活性测试结果表明, 目标化合物对大肠杆菌、 金黄色葡萄球菌、 枯草芽孢杆菌和白色念珠菌均显示出良好的抑菌活性. 化合物6g对大肠杆菌、 金黄色葡萄球菌、 枯草芽孢杆菌和白色念珠菌的最小抑菌浓度分别达到2, 8, 32和8 μg/mL, 抑菌效果接近或优于对照药物三氯生和氟康唑. 利用Autodock程序研究了目标化合物(6a~6i)与大肠杆菌烯脂酰还原酶(FabⅠ)受体蛋白分子的相互作用和结合自由能变化规律.

Synthesis and Antibacterial Activities of 3-S-(β-D-Glucosides)-1,2,4-triazole†

Nine novel compounds of 5-substituted-phenyl-4-amino-3-S-(β-D-glucopyranosyl)-1,2,4-triazole(6a—6i) were synthesized from 5-substituted phenyl-4-amino-3-ylsulfanyl-4H-1,2,4-triazol by glycosylation and then by deacetylate in the system of sodium methylate, methanol and dichloromethane. Their structures were confirmed by ¹H NMR, ¹³C NMR, IR and HRMS spectroscopy. The results of preliminary bioassay showed that most of the tested compounds display variable inhibitory activity against Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Monilia albican. Especially, the compound 6g had the strongest antibacterial activity with minimum inhibitory concentration of 2, 8, 32, 8 μg/mL against the four tested strains respectively which are similar to or higher than those of the controlled drug fluconazole or triclosan. The interaction and binding free energy of compounds 6a—6i with FabⅠ were studied by Autodock.