Tanaka Toru, Kawase Masami, Tani Satoru
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan.
Bioorg Med Chem. 2004 Jan 15;12(2):501-5. doi: 10.1016/j.bmc.2003.10.017.
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.
评估了多种α-羟基酮（1-13）和α-二酮（14-20）对刀豆脲酶的影响。在所测试的13种α-羟基酮（1-13）中，2,2'-噻吩因（10）（IC50 = 0.18 mM）、糠偶因（9）（IC50 = 0.36 mM）、2-羟基-1-苯乙酮（5）（IC50 = 0.47 mM）和丙酮醇（1）（IC50 = 2.9 mM）对该酶表现出强效抑制活性，与羟基脲（IC50 = 0.1 mM）相当。2-巯基乙醇或二硫苏糖醇可完全阻断其抑制作用。镍离子以剂量依赖方式影响5和9的抑制作用，但不影响1和10的抑制作用。另一方面，相应的α-二酮，如2,2'-噻吩二酮（20）、糠偶酰（19）和苯甲酰甲醛（14）对脲酶几乎没有或没有抑制能力。我们首次证明，一些α-羟基酮衍生物可能通过与活性位点中的半胱氨酰残基结合而表现出脲酶抑制活性。
