Ligand-based 3D-QSAR studies of diaryl acyl-sulfonamide analogues as human umbilical vein endothelial cells inhibitors stimulated by VEGF.

Diaryl acylsulfonamide derivatives were reported as Human Umbilical Vein Endothelial cell (HUVEC) inhibitors, stimulated by Vascular Endothelial Growth Factor (VEGF). VEGF has angiogenic property to cause colorectal cancer. A ligand-based 3D-QSAR technique was carried out on diaryl acylsulfonamide derivatives by using Comparative Molecular Field Analysis (CoMFA) studies to find relations between biological activities of inhibitors and their structures. In absence of binding mechanism for the ligand with VEGF receptor, current study hopes to shed some light on the inhibition mechanism of the ligands with HUVEC. 3D-QSAR technique was applied to a set of fifty ligands in order to facilitate the design of more potent inhibitors. However, the maximum cross-validated correlation coefficient value was found to be 0.417. The value is relatively low when compared to the usual acceptable cross-validated correlation coefficient, but no further improvements were observed by applying different available options. Therefore, the final model was used for further analysis. Additionally, the resulted CoMFA model was validated by an external set of 10 compounds yielding surprisingly, a satisfactory correlation coefficient value (r(2) (pred) ) 0.80. Moreover, the analysis of the individual generated 3D contours helped in understanding the possible structural modifications of molecules to improve the inhibitory potency.