Tomasić Tihomir, Zidar Nace, Rupnik Veronika, Kovac Andreja, Blanot Didier, Gobec Stanislav, Kikelj Danijel, Masic Lucija Peterlin
University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia.
Bioorg Med Chem Lett. 2009 Jan 1;19(1):153-7. doi: 10.1016/j.bmcl.2008.10.129. Epub 2008 Nov 5.
Mur ligases catalyze the biosynthesis of the UDP-MurNAc-pentapeptide precursor of peptidoglycan, an essential polymer of bacterial cell-wall. They constitute attractive targets for the development of novel antibacterial agents. Here we report on the synthesis of a series of 2,4-diaminoquinazolines, quinazoline-2,4(1H,3H)-diones, 5-benzylidenerhodanines and 5-benzylidenethiazolidine-2,4-diones and their inhibitory activities against MurD from Escherichia coli. Compounds (R)-27 and (S)-27 showed inhibitory activity against MurD with IC(50) values of 174 and 206 microM, respectively, which makes them promising starting points for optimization.
Mur连接酶催化肽聚糖的UDP-MurNAc-五肽前体的生物合成，肽聚糖是细菌细胞壁的一种重要聚合物。它们是开发新型抗菌剂的有吸引力的靶点。在此，我们报告了一系列2,4-二氨基喹唑啉、喹唑啉-2,4(1H,3H)-二酮、5-亚苄基硫代罗丹宁和5-亚苄基噻唑烷-2,4-二酮的合成及其对大肠杆菌MurD的抑制活性。化合物(R)-27和(S)-27对MurD显示出抑制活性，IC(50)值分别为174和206 microM，这使其成为有前景的优化起点。
