论文部分内容阅读
目的:建立关于salvinorin A型结构的C-12取代衍生物对KOPR的亲和力参数(LogKi)及效能参数(LogEC50)的分子结构与活性关系模型.方法:通过采用与多元线性回归分析相结合的遗传算法技术,结合量子化学参数(最低未占分子轨道能级ELUMO,C-7及C-14原子电荷qC7与qC14),建立鼠尾草A型结构的C-12取代衍生物的结构与活性关系模型.结果 与结论:两模型相关系数分别为0.911和0.951.研究表明鼠尾草A型结构C-12取代衍生物对KOPR的LogKi值随参数ELUMO的减少及参数qC14的增大而增大;LogEC50值随参数ELUMO的减少及参数qC7的增大而增大.“,”The natural product salvinorin A,a high affinity and highly selective agonist at the κ opioid receptor (KOPR),has been used as a lead compound for the design of selective KOPR agonists and antagonists.For the first time,quantitative structure-activity relationship(QSAR) models for affinities(LogKi) and potencies(LogEC50) of C-12 substituted salvinorin A derivatives at the KOPR were developed by means of genetic algorithm(GA) combined with multiple linear regression analysis (MLRA) technique.The models of LogKi and LogEC50 based on quantum chemical descriptors(the energy of the lowest unoccupied molecular orbital,ELUMO,atomic charges on C-7 and C-14,qc7 and qC14) have correlation coefficients of 0.911 and 0.951,respectively.The studies suggested that the parameter LogKi of C-12 substituted salvinorins at the KOPR increases with the decreasing ELUMO and increasing qC14,and the parameter LogEC50 increases with the decreasing ELUMO and increasing qC7.