2-Mercaptomethyl-thiazolidines use conserved aromatic-S interactions to achieve broad-range inhibition of metallo-β-lactamases.

ABSTRACT: Infections caused by multidrug resistant (MDR) bacteria are a major public health threat. Carbapenems are among the most potent antimicrobial agents that are commercially available to treat MDR bacteria. Bacterial production of carbapenem-hydrolysing metallo-β-lactamases (MBLs) challenges their safety and efficacy, with subclass B1 MBLs hydrolysing almost all β-lactam antibiotics. MBL inhibitors would fulfil an urgent clinical need by prolonging the lifetime of these life-saving drugs. Here we report the synthesis and activity of a series of 2-mercaptomethyl-thiazolidines (MMTZs), designed to replicate MBL interactions with reaction intermediates or hydrolysis products. MMTZs are potent competitive inhibitors of B1 MBLs in vitro (e.g., K _i = 0.44 μM vs.</

SUBMITTER: Rossi MA 

PROVIDER: S-EPMC8179362 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature