四种中药单体选择性抑制环氧合酶-2活性的评价  

Evaluation of Selective Inhibition of Cyclooxygenase-2 Activity by Four Chinese Herbal Monomers

作　　者：殷晓芹[1] 王新杨 徐新[1] 王静[1] 袁浩亮 YIN Xiao-qin;WANG Xin-yang;XU Xin;WANG Jing;YUAN Hao-liang(Department of Pharmacy,Affiliated Hospital of Nantong University;College of pharmacy,Nantong University,Nantong 226001,China;New drug research center,China pharmaceutical university,Nanjing 210009,China)

机构地区：[1]南通大学附属医院药学部 [2]南通大学药学院,南通226001 [3]中国药科大学新药研究中心,南京210009

出　　处：《天然产物研究与开发》2018年第10期1769-1775,共7页Natural Product Research and Development

基　　金：南通市科技计划(MS12015052)

摘　　要：为研究COX-2与中药抗肿瘤多药耐药的相关性,通过体外酶反应筛选实验,测定姜黄素、青藤碱、牡荆素、芹菜素对环氧合酶-1(COX-1)、环氧合酶-2(COX-2)的活性抑制作用,使用选择性指数(COX-1的IC50/COX-2的IC50)评价其COX-2活性的选择性,该实验结果显示:这四种物质对COX-2选择性指数依次为:牡荆素128. 71、姜黄素16. 24、芹菜素8. 45、青藤碱3. 55。并首次用分子对接相关数据中对接分子的对接内能及其与分子酶结合能差异性大小比较,评价了这四种物质对COX-2选择性活性,所得分子选择性结果与体外酶反应实验结果相吻合。从抑制活性和对COX-2选择性指数综合评价,牡荆素为较优化合物,可作为新的对COX-2有更高选择性活性的先导化合物。In order to investigate the action of traditional Chinese medicine on tumor multidrug resistance,the inhibition activities of curcumin,sinomenine,vitexin,and celery on COX-2(cyclooxygenase-2)versus COX-1(cyclooxygenase-1)were determined by in vitro enzymatic reaction experiments,using the selective index(COX-1 IC50/COX-2 IC50)to evaluate the selective inhibition activity against COX-2.The experimental results indicated that the selectivity index values of the four compounds against COX-2 are 128.71 for vitexin,16.24 for curcumin,8.45 for apigenin,and 3.55 for sinomenine,respectively.For molecular docking,the comparison of the four compounds for the docking molecule enzyme binding energy and docking molecules internal energy in the related molecular docking data was firstly used to evaluate the selective inhibition activity of the four compounds against COX-2.The molecular docking results are consistent with the in vitro enzymatic reaction results,which show that vitexin is more potent than other compounds against COX-2.These findings suggest that vitexin is the optimal compound which can be used as the lead compound for a new COX-2 inhibitors with more selective activity.

关 键 词：分子对接 天然化合物 环氧合酶-2 选择性抑制 肿瘤多药耐药性 

分 类 号：R961[医药卫生—药理学]