新型1,2,4-三唑并[3,4-b]-1,3,4-噻二唑类化合物的合成、抗菌活性及与FabⅠ作用的分子模拟  

Synthesis,Antibacterial Activity and Molecular Simulation with FabⅠ of a Series of Novel 1,2,4-Triazolo[3,4-b]-1,3,4-thiadiazoles

作　　者：王美君[1] 卢俊瑞[1] 辛春伟[1] 刘金彪[1] 穆江蓓[1] 张贺[1] 张瑞波[1] 杨旭云[1] 王宏韫 

机构地区：[1]天津理工大学化学化工学院,天津300384

出　　处：《高等学校化学学报》2015年第3期469-476,共8页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:21176194;21476174)资助~~

摘　　要：以3-芳基/烷基-4-氨基-5-巯基-1,2,4-三唑为原料,经过环化和糖化反应,设计合成了10个未见报道的化合物3-芳基/烷基-6-S-2',3',4',6'-四-O-乙酰基-β-D-吡喃葡萄糖基-1,2,4-三唑并[3,4-b]-1,3,4-噻二唑(3a^3j),其结构经核磁共振波谱、高分辨质谱和红外光谱确认.生物活性测试表明,所有化合物均对大肠杆菌、金黄色葡萄球菌、枯草芽孢杆菌和白色念株菌表现出一定的抗菌活性,其中化合物3c对4种测试菌株的最小抑菌浓度(MIC)最低,且接近于氟康唑的参照数据,具有较强的抗菌活性.利用Auto Dock 4.0程序研究了目标化合物3a^3j与大肠杆菌FabⅠ受体蛋白分子的相互作用和结合自由能变化规律.Ten novel compounds of 3-alkyl/aryl-6-S-（2＇,3＇,4＇,6＇-tetra-O-acetyl-fl-D-glcopyranosyl）-1 ,2,4- triazolo [ 3,4-b ] -1,3,4-thiadiazoles were designed and synthesized from 3-alkyl/aryl-4-amino-5-mercapto-1,2, 4-triazoles. The structures of all the compounds were confirmed by means of ^1H NMR, ^13C NMR, HRMS and IR. The preliminary bioassay showed that all target compounds possessed efficient antibacterial activities on Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Monilia albican. Especially, the compound 3c had strong antibacterial by the lowest minimal inhibitory concentration （MIC） values on the four tested strains which were close to those of the controlled drug fluconazole. The interaction and binding free energy of the tar- get compounds（3a--3j） with Fab I were studied by AutoDock 4.0.

关 键 词：糖苷 1 2 4-三唑并[3 4-b]-1 3 4-噻二唑 抗菌活性 FabⅠ受体蛋白 

分 类 号：O626.26[理学—有机化学]