meta-Substituted benzenesulfonamide: a potent scaffold for the development of metallo-β-lactamase ImiS inhibitors.

ABSTRACT: Metallo-β-lactamase (MβL) ImiS contributes to the emergence of carbapenem resistance. A potent scaffold, meta-substituted benzenesulfonamide, was constructed and assayed against MβLs. The twenty-one obtained molecules specifically inhibited ImiS (IC₅₀ = 0.11-9.3 μM); 2g was found to be the best inhibitor (IC₅₀ = 0.11 μM), and 1g and 2g exhibited partially mixed inhibition with K _i of 8.0 and 0.55 μM. The analysis of the structure-activity relationship revealed that the meta-substitutes improved the inhibitory activity of the inhibitors. Isothermal titration calorimetry (ITC) assays showed that 2g reversibly inhibited ImiS. The benzenesulfonamides exhibited synergistic antibacterial effects against E. coli<

SUBMITTER: Liu Y 

PROVIDER: S-EPMC7412727 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature