α-Hydroxyketones as inhibitors of urease

• DOI: 10.1016/j.bmc.2003.10.017
• Publication Date: 2003-12-10T12:22:49Z
• Authors: Toru Tanaka; Masami Kawase; Satoru Tani
• Keywords: Inhibitory Concentration 50; Binding Sites; Dose-Response Relationship, Drug; Nickel; Drug Evaluation, Preclinical; Enzyme Inhibitors; Ketones; Urease; 01 natural sciences; 0104 chemical sciences; 3. Good health

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.