Bi Fangchao, Ji Shengli, Venter Henrietta, Liu Jingru, Semple Susan J, Ma Shutao
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, China.
ReaLi Tide Biological Technology (Weihai) Co. Ltd., East Longhai Road & South Yangguang Road, Nanhai New District, Weihai 264207, China.
Bioorg Med Chem Lett. 2018 Mar 1;28(5):884-891. doi: 10.1016/j.bmcl.2018.02.001. Epub 2018 Feb 2.
3-Methoxybenzamide (3-MBA) derivatives have been identified as novel class of potent antibacterial agents targeting the bacterial cell division protein FtsZ. As one of isosteres for the amide group, 1,2,3-triazole can mimic the topological and electronic features of the amide, which has gained increasing attention in drug discovery. Based on these considerations, we prepared a series of 1H-1,2,3-triazole-containing 3-MBA analogues via isosteric replacement of the terminal amide with triazole, which had increased antibacterial activity. This study demonstrated the possibility of developing the 1H-1,2,3-triazole group as a terminal amide-mimetic element which was capable of both keeping and modulating amide-related bioactivity. Surprisingly, a different action mode of these new 1H-1,2,3-triazole-containing analogues was observed, which could open new opportunities for the development of antibacterial agents.
3-甲氧基苯甲酰胺（3-MBA）衍生物已被鉴定为一类新型的强效抗菌剂，其靶向细菌细胞分裂蛋白FtsZ。作为酰胺基团的电子等排体之一，1,2,3-三唑可以模拟酰胺的拓扑和电子特征，这在药物发现中越来越受到关注。基于这些考虑，我们通过用三唑对末端酰胺进行等排取代，制备了一系列含1H-1,2,3-三唑的3-MBA类似物，这些类似物具有增强的抗菌活性。本研究证明了将1H-1,2,3-三唑基团开发为末端酰胺模拟元件的可能性，该元件能够保持和调节与酰胺相关的生物活性。令人惊讶的是，观察到这些含新型1H-1,2,3-三唑的类似物具有不同的作用模式，这可能为抗菌剂的开发带来新的机遇。
