7cjl

Publication Abstract from PubMed

beta-Lactam antibiotic resistance mediated by metallo-beta-lactamases (MBL) has threatened global public health. There are currently no available inhibitors of MBLs for clinical use. We previously reported the ruthenium-catalyzed meta-selective C-H nitration synthesis method, leading to some meta-mercaptopropanamide substituted aryl tetrazoles as new potent MBL inhibitors. Here, we described the structure-activity relationship of meta- and ortho-mercaptopropanamide substituted aryl tetrazoles with clinically relevant MBLs. The resulting most potent compound 13a showed IC50 values of 0.044 muM, 0.396 muM and 0.71 muM against VIM-2, NDM-1 and IMP-1 MBL, respectively. Crystallographic analysis revealed that 13a chelated to active site zinc ions via the thiol group and interacted with the catalytically important residues Asn233 and Tyr67, providing further structural information for the development of thiol based MBL inhibitors.

Discovery of mercaptopropanamide-substituted aryl tetrazoles as new broad-spectrum metallo-beta-lactamase inhibitors.,Yan YH, Chen J, Zhan Z, Yu ZJ, Li G, Guo L, Li GB, Wu Y, Zheng Y RSC Adv. 2020 Aug 25;10(52):31377-31384. doi: 10.1039/d0ra06405j. eCollection, 2020 Aug 21. PMID:35520685^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.