Lewis David F V
School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK.
Inflammopharmacology. 2003;11(1):43-73. doi: 10.1163/156856003321547112.
Quantitative structure-activity relationships (QSARs) within substrates, inducers and inhibitors of cytochromes P450 involved in xenobiotic metabolism are reported, together with QSARs associated with induction, inhibition and metabolic rate. The importance of frontier orbitals and shape descriptors, such as planarity (estimated by the area/depth(2) parameter) and rectangularity (estimated by the length/width parameter) is discussed, particularly in the context of the COMPACT system which discriminates between several P450 families associated with the activation and detoxication of xenobiotics. The use of parameters, particularly those derived from homology modelling of mammalian (especially human) P450s that are involved in exogenous metabolism, in generating QSARs for P450 substrates is discussed in the context of explaining differences in the binding affinities of human P450 substrates which are pharmacologically active.
本文报道了参与异源物代谢的细胞色素P450底物、诱导剂和抑制剂中的定量构效关系（QSARs），以及与诱导、抑制和代谢速率相关的QSARs。讨论了前沿轨道和形状描述符的重要性，如平面度（由面积/深度(2)参数估计）和矩形度（由长度/宽度参数估计），特别是在COMPACT系统的背景下，该系统可区分与异源物激活和解毒相关的几个P450家族。在解释具有药理活性的人P450底物结合亲和力差异的背景下，讨论了参数的使用，特别是那些源自参与外源代谢的哺乳动物（尤其是人类）P450同源建模的参数，用于生成P450底物的QSARs。
