Identification of α-mangostin as a potent inhibitor of β-lactamase OXA-48

The production of carbapenemases is a significant mechanism contributing to carbapenem resistance in Enterobacteriaceae. Among these carbapenemases, OXA-48 presents a distinct challenge and threat, as most β-lactamase inhibitors do not effectively inhibit its activity. In this study, we investigated the inhibitory potential of α-mangostin against OXA-48 with an IC₅₀ value of 0.52 μM. Enzyme activity assays demonstrated that α-mangostin inhibited OXA-48 reversibly through a non-competitive and dose-dependent inhibition mode. The docking analysis revealed that the 7-hydroxyl group of α-mangostin formed hydrogen bonds with Thr197 and Trp222, whereas the 5-hydroxyl group and the 4-carbonyl group interacted with Lys116 and Met115. Our study indicates that α-mangostin exhibits significant inhibition against OXA-48 and holds promise as a potential compound for the development of β-lactamase inhibitors.