摘要
细胞色素Ｐ４５０（Ｐ４５０，Ｅｃ１．１４．１４．１）是一种十分重要的催化氧化反应的酶。本文测定了１２个对氨基苯甲酸酯同系物与Ｐ４５０相互作用而形成Ｐ４５０代谢中间体络合物的活性，用半经验分子轨道法ＭＮＤＯ－ＰＭ３计算得到了这些同系物的分子轨道指数，并用逐步多元回归分析法导出了活性与分子轨道指数及正辛醇／水分配系数的对数值（ＬｏｇＰ）之间的定量结构与活性关系（ＱＳＡＲ）。结果表明：对氨基苯甲酸脂同系物形成Ｐ４５０代谢中间体络合物的活性与原子净电荷的绝对值之和（∑Ｑ）和ＬｏｇＰ均具有很好的抛物线型相务性，同时，ＬｏｇＰ与∑Ｑ之间也存在相当好的相关性。
Twelve p-aminobenzoate homologues were tested for their activities of forming cytochrome P_(450) (P_(450)) metabolic intermediate complex. The semiempirical self-consistent field molecular orbital calculation MNDO-PM3 method was utilized to obtain the molecular orbital indexes of the 12 p-aminobenzoates investigated. Stepwise multiple regression analyses were then utilized to obtain the quantitative structure-activity relationships (QSARs) between the activites of forming P_(450) metabolic intermediate complex and the above molecular orbital indexes or the octanol/water partition coefficients. The results showed that the activities for p-aminobenzoates to form P_(450) metabolic intermediate complex were well correlated with the sum of the absolute values of the atomic charges (∑Q) and LogP. Significant correlations were observed between LogP and ∑Q.
基金
中国医学科学院青年科学基金
国家自然科学基金
分子轨道计算获中国科学院计算机化学开放实验室资助
关键词
细胞色素
对氨基
苯甲酸酯
络合物
Cytochrome P_(450)
p-aminobenzoates
Metabolic-intermediate complex
Quantitative structure-activity relationship
MNDO-PM3
