Tanaka Toru, Kawase Masami, Tani Satoru
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan.
Life Sci. 2003 Oct 24;73(23):2985-90. doi: 10.1016/s0024-3205(03)00708-2.
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.
评估了多种α,β-不饱和酮对刀豆脲酶的作用。在测试的35种化合物中，2-环庚烯-1-酮（1）、2-环己烯-1-酮（2）、2-环戊烯-1-酮（3）和5,6-二氢-2H-吡喃-2-酮（4）对该酶表现出强效抑制活性。最有效的化合物（1）（IC50 = 0.16 mM）显示出与羟基脲（IC50 = 0.095 mM）相似的抑制效力。2-巯基乙醇或二硫苏糖醇可显著降低1、2、3和4的抑制作用。这些数据表明，α,β-不饱和酮可能通过蛋白质SH基团与α,β-不饱和羰基双键的类似迈克尔加成反应来抑制脲酶活性。
