University of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000 Ljubljana, Slovenia.
ChemMedChem. 2010 Feb 1;5(2):286-95. doi: 10.1002/cmdc.200900449.
Mur ligases participate in the intracellular path of bacterial peptidoglycan biosynthesis and constitute attractive, although so far underexploited, targets for antibacterial drug discovery. A series of hydroxy-substituted 5-benzylidenethiazolidin-4-ones were synthesized and tested as inhibitors of Mur ligases. The most potent compound 5 a was active against MurD-F with IC(50) values between 2 and 6 microm, making it a promising multitarget inhibitor of Mur ligases. Antibacterial activity against different strains, inhibitory activity against protein kinases, mutagenicity and genotoxicity of 5 a were also investigated, and kinetic and NMR studies were conducted.
Mur 连接酶参与细菌肽聚糖生物合成的细胞内途径，是具有吸引力的、尽管尚未充分开发的抗菌药物发现靶标。我们合成了一系列羟基取代的 5-亚苄基噻唑烷-4-酮，并将其作为 Mur 连接酶抑制剂进行了测试。最有效的化合物 5a 对 MurD-F 的抑制活性在 2 到 6 微摩尔之间，使其成为 Mur 连接酶的有前途的多靶标抑制剂。我们还研究了 5a 对不同菌株的抗菌活性、对蛋白激酶的抑制活性、致突变性和遗传毒性，并进行了动力学和 NMR 研究。
