Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji-Rongcheng Center for Biomedicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Microbiol Res. 2022 Aug;261:127079. doi: 10.1016/j.micres.2022.127079. Epub 2022 May 27.
New Delhi metallo-β-lactamase-1 (NDM-1) can hydrolyze almost all antibiotics of the β-lactam group, resulting in the generation of multidrug resistant bacteria. Besides its broad hydrolytic activity, pathogens expressing NDM-1 often harbor other antibiotic-resistant genes, further promoting the pervasion of multi-resistant clinical isolates and making clinically available drugs scantier. Despite the urgent need for NDM-1 inhibitors, there is no approved drug in clinic. Here, we summarize NDM-1 inhibitors developed since 2018, classify these compounds by chemical scaffolds, and propose some inconsistencies and notable problems among these studies, which are expected to benefit future research.
新德里金属β-内酰胺酶-1(NDM-1)几乎可以水解β-内酰胺类的所有抗生素,导致产生多药耐药菌。除了广泛的水解活性外,表达 NDM-1 的病原体通常还携带其他抗生素耐药基因,进一步促进了多耐药临床分离株的传播,使临床可用的药物更加稀缺。尽管急需 NDM-1 抑制剂,但目前临床上还没有批准的药物。在这里,我们总结了自 2018 年以来开发的 NDM-1 抑制剂,按化学支架对这些化合物进行分类,并提出了这些研究中的一些不一致和值得注意的问题,预计这将有助于未来的研究。