关键词: HMG-CoA还原酶抑制剂, 三维药效团, 数据库搜索

Abstract: A three-dimensional pharmacophore model of 3-hydro-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors (RI)was developed based on 21 HMG-CoAreductase inhibitors froma rat liver. The selected training set had great diversity in both molecular structure and bioactivity as required by HypoGen program in the Catalyst software. The inhibitors in training set showed HMG-CoA RI inhibiting activity with IC50 values of 0.3-8000 nmol·L-1. The best statistical hypothesis, consisting of four features, one hydrogen-bond acceptor, one hydrogen-bond donor, one ring aromatic feature, and one hydrophobic point, had a correlation coefficient of 0.8883, a root-mean-square (RMS) deviation of 1.269, a Fixed cost of 88.75, a Total cost of 111.5, and a Configuration cost of 16.98, this hypothesis had highly predictive ability. The predictive ability was approved by the results of the activity estimated by mapping the compounds of the testing set with it. The cross-validation provided strong confidence on this hypothesis. This pharmacophore model can contribute to the finding and designing of new-type HMG-CoA reductase inhibitors, and to the development of traditional Chinese medicine and materia medica.

Key words: HMG-CoA reductase inhibitor, Pharmacophore, Database searching