Pharmacophore Model Construction of Endothelins A Receptor Antagonist / 世界科学技术-中医药现代化

ABSTRACT

This study was aimed to construct the pharmacophore models of endothelins A receptor antagonist in the application of screening traditional Chinese medicine (TCM) database for novel ETA Receptor antagonists. Qualitative and quantitative hypotheses were generated by HipHop and HypoGen separately on the basis of 36 compounds with antagonistic action on Endothelins A Receptor expressed in the aortic smooth muscle cells of rats. Database searching method was used to evaluate the generated hypotheses. The optimum hypotheses were used to search TCM database. The results showed that optimum qualitative hypothesis is with six features, which were one aromatic ring, one hydrogen-bond acceptors, one negative ionizable group and three hydrophobic groups, and the CAI value of 103.94. The optimum quantitative hypothesis is with six features, which were one aromatic ring, one hydrogen-bond acceptor, one negative ionizable group, two hydrophobic groups and one exclusive volume, and the CAI value of 45.96. Sixteen compounds from TCM were found in the database searching with the quantitative hy-pothesis. It was concluded that the pharmacophores are reliable and can be used to screen database for novel E-TA inhibitors. The qualitative and quantitative hypothesis can be used to screen database for active compounds and to predict the activity respectively.