染料木素及其衍生物的尿素酶抑制活性与作用机制  

Urease inhibitory activity and mechanism of genistein and its derivatives

作　　者：郑大贵[1] 彭知云[2] 王旭东[2] 周银[2] 黄莘[2] 肖竹平[1,2] 

机构地区：[1]上饶师范学院,江西省普通高校应用有机化学重点实验室,上饶334001 [2]吉首大学化学化工学院,吉首416000

出　　处：《中国新药杂志》2013年第8期951-955,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金(81273382);江西省普通高校重点实验室科技计划项目(2007-402);湖南省自然科学基金(11JJ3113)

摘　　要：目的:观察染料木素及其衍生物对幽门螺杆菌尿素酶的抑制作用,探讨染料木素抑制尿素酶的作用机制。方法:采用靛酚法测定目标化合物的尿素酶抑制活性;双曲线法研究目标化合物抑制尿素酶的作用机制;双倒数曲线的斜率对抑制剂浓度作图法确定目标化合物的动力学常数Ki。结果:染料木素的羟基被甲氧基等取代,将导致活性的降低;染料木素抑制幽门螺杆菌尿素酶的IC50达13.7μmol.L-1,活性与阳性对照乙酰氧肟酸相当;染料木素是尿素酶的非竞争抑制剂,Ki为13.4μmol.L-1。结论:染料木素具有良好的抑制幽门螺杆菌尿素酶的活性,长期食用富含染料木素的食物,将有助于防止消化性溃疡的发生或对消化性溃疡有辅助治疗的作用;染料木素可以作为寻找新型高效尿素酶抑制剂的先导化合物。Objective ： To evaluate the inhibitory activity of genistein and its derivatives against Helicobacter pylori urease, and to explore the inhibition mechanism. Methods： Urease activity was determined by using the in- dophenol method as described by Weatherburn; the inhibition pattern of genistein was determined by Lineweaver- Burk plot ; Ki value was calculated from a plotting of the slopes of the Lineweaver-Burk plot versus the concentration of the inhibitor. Results： Substitution of methoxyl group for hydroxyl group of genistein led to an insignificant de- crease in inhibitory activity against H. pylori urease; genistein showed potent urease inhibitory activity with IC50 of 13.7 μmol·L^-1, which was lower than that of the positive control （ acetohydroxamic acid） ; genistein was an un- competitive inhibitor of H. pylori urease with Ki of 13.4 μmol·L^-1. Conclusion： Genistein is a potent inhibitor a- gainst H. pylori urease. Food with high-content of genistein is therefore helpful to digestive disease therapy or pre- vention. Genistein can be used as a lead compound to find novel potent urease inhibitors.

关 键 词：染料木素 合成 幽门螺杆菌 尿素酶抑制剂 作用机制 

分 类 号：R914.4[医药卫生—药物化学]