时间：2026-07-05
本文（Discovery of 3-methacylic acid substituted benzoxaboroles as dual metallo- and serine-β-lactamase inhibitors）原载Eur. J. Med. Chem，由四川大学李国菠教授等科研人员创作，系四川智慧社会智能治理重点实验室智慧法治研究所的系列学术成果。本网站后续将持续分享实验室的系列学术成果，欢迎大家阅读。
Carbapenem resistance is an ongoing clinical problem, largely driven by production of evolved serine β-lactamases (SBLs) and metallo-β-lactamases (MBLs). We here report a series of new 3-methacrylic acid-substituted benzoxaboroles as dual MBL/SBL inhibitors. Structure-activity relationship studies showed that the new compounds manifested nanomolar inhibition to the SBLs KPC-2 and OXA-48, and single-digit micromolar inhibition to the MBLs VIM-2, NDM-1, and NDM-5. Co-crystallographic analyses revealed their binding modes with VIM-2 and OXA-48, which are similar as those of taniborbactam and xeruborbactam. Bacterial assays demonstrated that compound 10 can potentiate meropenem against multidrug-resistant Gram-negative strains. This work provides new lead compounds and structural basis for developing new drug candidates against MBL/SBL-mediated carbapenem resistance.
Liang, G.-Q.; Jiang, Y.-Y.; Han, C.-L.; Wang, Y.; Wang, S.-Y.; Chen, Y.-T.; Li, G.; Li, G.-B.; Xiao, Y.-C. Discovery of 3-methacylic acid substituted benzoxaboroles as dual metallo- and serine-β-lactamase inhibitors. Eur. J. Med. Chem. 2025, 293, 117723.（论文下载）
