Discovery of Quercetin and Its Analogs as Potent OXA-48 Beta-Lactamase Inhibitors.

ABSTRACT: Carbapenem resistance in Enterobacteriaceae caused by OXA-48 β-lactamase is a growing global health threat and has rapidly spread in many regions of the world. Developing inhibitors is a promising way to overcome antibiotic resistance. However, there are few options for problematic OXA-48. Here we identified quercetin, fisetin, luteolin, 3',4',7-trihydroxyflavone, apigenin, kaempferol, and taxifolin as potent inhibitors of OXA-48 with IC₅₀ values ranging from 0.47 to 4.54 μM. Notably, the structure-activity relationship revealed that the substitute hydroxyl groups in the A and B rings of quercetin and its structural analogs improved the inhibitory effect against OXA-48. Mechanism studies including enzymatic kinetic assay, isothermal titration calorimetry (ITC), and surfac

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC9258905 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature