Jiang Yongwei, Lin Weixin, Tan Subei, Wang Yuxuan, Wu Wei, Lu Zhigang
Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China.
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
ACS Omega. 2023 Jul 25;8(31):28511-28518. doi: 10.1021/acsomega.3c02879. eCollection 2023 Aug 8.
A series of novel vancomycin analogues with quaternary ammonium moieties have been designed and synthesized for fighting with clinically isolated drug-resistant bacteria. Partial target molecules exhibited potent activity against the tested strains. Among all of the compounds, a triazole quaternary ammonium vancomycin (QAV) derivative QAV-a1 exerted the best antibacterial activities. QAV-a1 was found to be 4- to 32-fold more efficacious than vancomycin against MRSA. Meanwhile, QAV-a1 showed a good pharmacokinetic profile with a half-life of 5.19 ± 0.10 h, which is longer than that of vancomycin (4.3 ± 1.9 h). These results provided guidance for the further exploitation of vancomycin derivatives against drug-resistant bacteria.
为对抗临床分离的耐药菌，已设计并合成了一系列带有季铵基团的新型万古霉素类似物。部分目标分子对受试菌株表现出强效活性。在所有化合物中，一种三唑季铵万古霉素（QAV）衍生物QAV-a1展现出最佳抗菌活性。发现QAV-a1对耐甲氧西林金黄色葡萄球菌（MRSA）的效力比万古霉素高4至32倍。同时，QAV-a1显示出良好的药代动力学特征，半衰期为5.19±0.10小时，比万古霉素的半衰期（4.3±1.9小时）更长。这些结果为进一步开发抗耐药菌的万古霉素衍生物提供了指导。
