Three-dimensional quantitative structure–activity relationship analyses of a series of cinnamamides

Abstract

A 3D-QSAR study was conducted on a series of cinnamamides with anticonvulsant activities using comparative molecular similarity indices analysis (CoMSIA) and comparative molecular field analysis (CoMFA). In the current work, all-space searching procedure was applied to minimize the field sampling process. The comparison of sensitivity of CoMFA and CoMSIA to the different space orientation showed that the CoMSIA q 2 values were less sensitive to the translations and rotations of the aligned molecules with respect to the lattice compared with CoMFA. After all-space searching calculations, we could come up with a good CoMSIA model ( q 2 and r 2 values equal to 0.742 and 0.917, respectively) and the validity of the model was confirmed by additional five compounds in the external test set. Contour surfaces for the molecular fields are presented. These results provide useful information in the characterization and identification of the potential mechanisms of intermolecular interactions between ligand and receptor.