Acta Phys. -Chim. Sin. ›› 2008, Vol. 24 ›› Issue (02): 301-306.doi: 10.3866/PKU.WHXB20080220

• ARTICLE • Previous Articles     Next Articles

Pharmacophore Model Generation of HMG-CoA Reductase Inhibitors

BAO Hong-Juan; ZHANG Yan-Ling; QIAO Yan-Jiang   

  1. School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, P. R. China
  • Received:2007-07-19 Revised:2007-11-22 Published:2008-01-26
  • Contact: QIAO Yan-Jiang

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