α-Hydroxyketones as inhibitors of urease Original Research Article

A variety of α-hydroxyketones (1–13) and α-diketones (14–20) were evaluated for their effect on the jack bean urease. Of 13 α-hydroxyketones (1–13) tested, 2,2′-thenoin (10) (IC50=0.18 mM), furoin (9) (IC50=0.36 mM), 2-hydroxy-1-phenylethanone (5) (IC50=0.47 mM) and acetol (1) (IC50=2.9 mM) showed potent inhibitory activity against the enzyme, comparable with hydroxyurea (IC50=0.1 mM). The inhibitory effects were completely blocked by 2-mercaptoethanol or dithiothreitol. A nickel ion influenced the inhibitory effects of 5 and 9 in a dose-dependent manner, but not of 1 and 10. On the other hand, the corresponding α-diketones such as 2,2′-thenil (20), furil (19) and PhCOCHO (14) exhibited little or no ability to inhibit the urease. We have demonstrated for the first time that some α-hydroxyketone derivatives show urease inhibitory activity, possibly by binding to cysteinyl residues in the active site.