QSAR and docking studies on Triazole Benzene Sulfonamides with human Carbonic anhydrase IX inhibitory activity

Cancer is the second leading cause of death worldwide, and breast cancer accounts for 2.09 million cases in the year 2018. Hypoxia-related human carbonic anhydrase IX enzyme was found to play a key role in metastasis also. In this view, quantitative structure activity relationship (QSAR) studies were carried out by QSARINS on triazole benzene sulfonamide derivatives for carbonic anhydrase IX inhibitory activity targeting breast cancer. A new scope to explore 3D-MoRSE descriptors in carbonic anhydrase inhibition has been initiated by this study. The best model 3 generated includes five variables MoRSEV22, MoRSEC17, MoRSEV1, MoRSEC4, and MoRSEE2 with statistical values R-2 = 0.7852, CCCtr = 0.8797, Q(LOO)(2) = 0.7237, Q2(LMO) = 0.7071, CCCcv = 0.8472, R-ext(2) = 0.7894, and CCCext = 0.8784. The developed QSAR model suggests that the atomic volume, atomic charges, and Sanderson's electronegativity play key roles and were extremely helpful in designing and optimizing the lead. Molecular docking studies were performed using Autodock v 4.2.6 and the residues of active site region involving both hydrophilic and hydrophobic parts interacted with best predicted active compounds 1d, 3e, 6f and 9f. The study leads to the development of new inhibitors targeting breast cancer.