Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK.
J Enzyme Inhib Med Chem. 2010 Oct;25(5):679-84. doi: 10.3109/14756360903514149.
The results of quantitative structure-activity relationship (QSAR) studies on inhibitors and substrates of cytochrome P450 2B (CYP2B) subfamily enzymes are reported. It was found that lipophilicity (in the form of log P) is the most important property for explaining the variations in inhibitory activity, and there are similarities between QSARs for both substrates and inhibitors for CYP2B6 (human), and also between those of other CYP2B enzymes, such as CYP2B1 (rat) and CYP2B4 (rabbit). Both linear and quadratic lipophilicity relationships are evidenced in human and other mammalian species, and the particular type of expression found is probably due to the nature of the compounds under investigation, as it is usually the homologous series which tend to show quadratic relationships in log P. The findings from QSAR studies can be rationalized by molecular modelling of the active site interactions with both P450 crystal structures and homology models of CYP2B subfamily enzymes.
报道了细胞色素 P450 2B（CYP2B）亚家族酶抑制剂和底物的定量构效关系（QSAR）研究结果。结果发现，亲脂性（以 log P 的形式）是解释抑制活性变化的最重要性质，CYP2B6（人）的底物和抑制剂的 QSAR 之间存在相似性，CYP2B1（大鼠）和 CYP2B4（兔）等其他 CYP2B 酶的 QSAR 之间也存在相似性。在人类和其他哺乳动物物种中都存在线性和二次亲脂性关系，并且发现的特定表达类型可能归因于所研究化合物的性质，因为通常是同系物在 log P 中表现出二次关系。QSAR 研究的结果可以通过与 P450 晶体结构和 CYP2B 亚家族酶的同源模型的活性位点相互作用的分子建模来合理化。
