论文部分内容阅读
目的:寻找新型、高效的幽门螺旋杆菌尿素酶抑制剂。方法:通过reformatsky反应和肟化反应合成新化合物3-羟基-3-(2-羟基-5-氯苯基)丙酰氧肟酸(Ⅵ);使用靛酚法测定其尿素酶抑制活性;利用双倒数法研究其抑制尿素酶的作用机制;采用双曲线斜率对抑制剂浓度作图法确定其动力学常数K_i。结果:Ⅵ抑制幽门螺杆菌尿素酶的IC_(50)达1.18μmol·L~(-1),活性比市场药乙酰氧肟酸(IC_(50)=17.0μmol·L~(-1))高一个数量级;Ⅵ是尿素酶的混合型抑制剂,表现出快速抑制行为,K_i为1.13μmol·L~(-1)。结论:Ⅵ是一种具有较高活性的新型尿素酶抑制剂,具有潜在的药用开发价值,可作为治疗幽门螺旋杆菌感染导致的胃炎、胃溃疡等疾病药物的先导化合物。
Objective: To find a new and efficient H. pylori urease inhibitor. Methods: The new compound 3-hydroxy-3- (2-hydroxy-5-chlorophenyl) propionyloxamic acid (Ⅵ) was synthesized by reformatsky reaction and oximation reaction; its urease inhibitory activity was determined by indophenol method; Double reciprocal method to study the mechanism of its inhibition of urease; Hyperbolic slope inhibitor concentration was used to determine the kinetic constants K_i. Results: Ⅵ inhibited the IC50 of Helicobacter pylori to 1.18 μmol·L -1, which was higher than that of the commercial drug acetohydroxamic acid (IC 50 = 17.0 μmol·L -1) An order of magnitude; Ⅵ is a mixed inhibitor of urease, showed rapid inhibition, K_i was 1.13μmol·L -1. Conclusion: Ⅵ is a novel urease inhibitor with high activity. It has potential value for medicinal development and can be used as a lead compound in the treatment of gastritis, gastric ulcer and other diseases caused by Helicobacter pylori infection.