新型抗菌剂:脂烯酰基酰基载体蛋白还原酶抑制剂的研究进展  

Progress in Enoyl-[acyl-carrier-protein] Reductase Inhibitors,a Novel Type of Antibacterial Agents

作　　者：王思袭[1] 周伟澄[1] 

机构地区：[1]上海医药工业研究院药物创新中心,上海200437

出　　处：《药学进展》2006年第8期341-349,共9页Progress in Pharmaceutical Sciences

基　　金：上海市科学技术委员会科研计划项目课题(04DZ05902;04JC14068)

摘　　要：简介脂烯酰基酰基载体蛋白还原酶在脂肪酸生物合成中的催化作用,综述其5类抑制剂即1,4-二取代咪唑类、2,9-二取代-1,2,3,4-四氢吡啶并[3,4-b]吲哚类、氨基吡啶类、吲哚萘啶酮类及3-氰基-4,6-二取代-2-吡啶硫醚类化合物的抗菌作用机制和构效关系。脂肪酸合成途径Ⅱ是大多数原核生物(如细菌)合成脂肪酸的方式,脂烯酰基酰基载体蛋白还原酶是催化细菌脂肪酸合成循环中最终步骤的酶,研究开发作用于该酶的抑制剂有可能发现新型抗菌药物。The catalyzing of enoyl-[acyl-carrier-protein] reductase Ⅰ （FabI） in the biosynthesis of fatty acid was briefly introduced. The mechanism of antibacterial action and structure-activity relationship of five kinds of FabI inhibitors, i.e., 1,4-disubstituted imidazoles, 2, 9-disubstituted-1,2, 3,4-tetrahydropyrido [ 3,4-b ] indoles, aminopyridines, indole naphthyridinones and 3-cyano-4, 6-disubstituted-2-pyridylthioethers, were reviewed. Fatty acid synthesis Ⅱ （FAS Ⅱ ） is the biosynthetic pathway for fatty acid in most prokaryotes, such as bacteria. FabI is the enzyme which catalyzes the ultimate step in bacterial FAS Ⅱ . Therefore the research and development of its inhibitors are helpful to the discovery of novel antibacterials.

关 键 词：脂烯酰基酰基载体蛋白还原酶抑制剂 抗菌剂 作用机制 结构修饰 构效关系 

分 类 号：R978.1[医药卫生—药品]