结构修饰的穿心莲对UGT2B7抑制能力的评价

Structure-inhibition Relationship of Andrographolide Derivative Towards UDP-glucuronosyltransferase(UGT)2B7

临床上穿心莲大多应用于治疗呼吸系统疾病、心血管系统疾病和胃肠道系统疾病等.现今,临床上多存在同时使用两种甚至两种以上的药物,引起体内代谢酶UGTs的代谢抑制,从而引发药物-药物相互作用.本实验主要研究由实验室合成的穿心莲内酯化合物A:zfx-45-7对UGT2B7酶的抑制作用,采用4-甲基伞形酮(4-MU)葡萄糖醛酸化抑制法,以4-MU作为底物对UGT2B7代谢穿心莲化合物的抑制能力做了初步的筛查,测得其残余活性小于20%,继续实验测定抑制常数K_1值为0.15μm0l/L,从而为进一步合成穿心莲药物做出理论和基础实验准备.

Clinically currently exist in much of taking 2 or more drugs simultaneously,which may cause the metabolism inhibition of the etabolic enzymes UGTs,and finally initiate a drug-drug interaction.This research studied mainly the inhibition ability of a laboratory synthesized andrographolide derivative zfx-45-7 against me UGT2B7,which has mainly used the 4-MU glucuronidation assay.We have used 4-MU as a substrate to achieve a preliminary screening of the inhibition ability of UGT2B7 against andrographolide derivative,and then further determined the K_1 value as 0.15 μmol/L,in order to further the theory and basic experiment prepared to creat drugs.