title: Alpha-hydroxyketones as inhibitors of urease.
abstract: A variety of alpha-hydroxyketones (1-13) and alpha-diketones (14-20) were evaluated for their effect on the jack bean urease. Of 13 alpha-hydroxyketones (1-13) tested, 2,2'-thenoin (10) (IC(50)=0.18 mM), furoin (9) (IC(50)=0.36 mM), 2-hydroxy-1-phenylethanone (5) (IC(50)=0.47 mM) and acetol (1) (IC(50)=2.9 mM) showed potent inhibitory activity against the enzyme, comparable with hydroxyurea (IC(50)=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 alpha-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 alpha-hydroxyketone derivatives show urease inhibitory activity, possibly by binding to cysteinyl residues in the active site.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Tanaka
authors.forename: Masami
authors.initials: M
authors.lastname: Kawase
authors.forename: Satoru
authors.initials: S
authors.lastname: Tani
mesh_terms: D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000737:chemistry* / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D014510:Urease / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007659:Ketones; D009532:Nickel; D014510:Urease