钒配合物的药理作用和理性药物设计  

The pharmacological/toxicological effects and rational drug design of vanadium complexes

作　　者：董雅琼 牛霞[1] 肖茹月[1] 张悦[1] 夏青[1] 杨晓达[1] 

机构地区：[1]北京大学天然和仿生药物国家重点实验室及药学院化学生物学系,北京大学医学部,北京100191

出　　处：《中国科学：化学》2017年第2期162-171,共10页SCIENTIA SINICA Chimica

基　　金：国家自然科学基金(编号:21571006,21271012);方正创新药物基金支持项目资助

摘　　要：自19世纪90年代以来,钒配合物的药物发现及其基础研究有了很大的进展,但仍然存在很多亟待解决的问题.本文综述了钒配合物的抗肿瘤、抗糖尿病作用和分子机制,及其潜在新作用——抗阿尔茨海默症的作用,也介绍了钒配合物的毒性作用及其机制研究.另外,本文在阐明其药理作用和毒性作用分子机理的基础上,综述了钒配合物的理性药物设计,包括基于与靶蛋白作用的钒配合物、基于BMOV先导化合物的钒配合物和基于抗氧化策略的钒配合物等.未来抗糖尿病钒配合物的理性药物设计的关键仍是如何平衡其潜在毒性与抗糖尿病药理活性,而通过抗氧化策略的钒配合物设计或许是解决这一关键问题的有效途径.Since 1990 s,great progress has been made in the studies of vanadium drag discovery and relevant fundamental researches.However,there remain many concerns to be clarified.In this review,studies on the anti-diabetic and anti-tumor effects of vanadium complexes and the relevant molecular mechanisms were summarized,the potential use for treatment of Alzheimer＇s disease was indicated,and the toxicity and mechanism of the vanadium complexes were also discussed.Based on the molecular mechanism of the pharmacological/toxicological effects of vanadium complexes,three strategies for rational vanadium drag design were discussed,i.e.structural designs based on interaction with vanadium binding proteins,BMOV as lead compound,and antioxidant incorporation.The key issue for rational drag design of anti-diabetic vanadium complexes will still be how to balance the potential toxicity and pharmacological activities,and antioxidant strategies may be an effective way to the solution.

关 键 词：钒配合物 糖尿病 阿尔茨海默症 PPAR AΒ 

分 类 号：O641.4[理学—物理化学]