Understanding the structural requirements of triarylethane analogues towards PDE-IV inhibitors: a molecular modeling study

Abstract

A three-dimensional quantitative structure activity relationship study has been performed on a series of 44 triarylethanes to determine the structural requirements for phosphodiesterase-IV (PDE-IV) enzyme inhibition. Considering the stereochemistry of the data set molecules and the varied types of alignments available, a total of seven models are presented. While most models were optimized to yield satisfactory r² and q² values, the best model was obtained with 29 molecules including all the R conformation with r² 0.996, q² 0.510 and r²_pred 0.744. A complementary molecular docking analysis is carried out considering the 29 stereochemically characterized set of molecules. The CoMFA maps and the docking studies were used to understand the structural requirements for the PDE-IV inhibition. These studies are expected to provide useful insights into the roles of various substitution patterns on the triarylethane skeleton and also help to design more potent compounds.