Urease inhibitory activity of simple alpha,beta-unsaturated ketones.
A variety of alpha,beta-unsaturated ketones were evaluated for their effect on the jack bean urease. Of 35 compounds tested, 2-cyclohepten-1-one (1), 2-cyclohexen-1-one (2), 2-cyclopenten-1-one (3), and 5,6-dihydro-2H-pyran-2-one (4) showed potent inhibitory activities against the enzyme. The most potent compound (1) (IC50=0.16 mM) showed similar inhibitory potency to hydroxyurea (IC50=0.095 mM). The inhibitory effects of 1, 2, 3, and 4 were significantly reduced by 2-mercaptoethanol or dithiothreitol. These data suggest that alpha,beta-unsaturated ketones inhibited the urease activity, possibly by a Michael-like addition of a protein SH group to the double bond of the alpha,beta-unsaturated carbonyl group.
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D007887:Fabaceae / Q000201:enzymology*; D006918:Hydroxyurea / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014510:Urease / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007659:Ketones; D014510:Urease; D006918:Hydroxyurea