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

Abstract

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 R2 = 0.7852, CCCtr = 0.8797, Q2LOO = 0.7237, Q2LMO = 0.7071, CCCcv = 0.8472, R2ext = 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.

Docking studies and molecular dynamics simulation of triazole benzene sulfonamide derivatives with human carbonic anhydrase IX inhibition activity

“…The residual values obtained using the attained QSAR model display that there was not much bioactivity deviation from the experimental inhibition value. 7 The selected QSAR model providing structural information helped in developing potent compounds with better CA IX inhibitory activity.…”

“…In our published research work, 7 a series of 70 compounds dataset containing 1,2,3-triazole benzene sulfonamide derivatives with human carbonic anhydrase IX inhibitory activity from the in vitro studies of P. K. Sharma et al 8–10 were subjected to QSARINS software for developing validated models using 3D-MoRSE molecular descriptors. The best QSAR model with MoRSE molecular descriptors thoroughly validated the dataset with efficient statistical parameters.…”

“…Fig. 1 display the leads generated from our previous work 7 along with their predicted bioactivities.…”

“…High computing power with graphic processing units is indeed beneficial for calculating molecular descriptors. Utilizing the best quantitative structure–activity relationship model generated in our published work, 7 the lead compounds with carbonic anhydrase IX inhibitory activity were considered as template ( Fig. 1 ) for investigating a novel series of triazole benzene sulfonamide derivatives with good predicted bioactivity.…”

Ligand based pharmacophore modelling and integrated computational approaches in the quest for small molecule inhibitors against hCA IX

“…24,25 The design and development of isoform-specic hCA inhibitors continue to be difficult task because of the high degree of structural similarity between the hCA isoforms and sequence similarities inside the active area. We have recently reported triazole benzene sulfonamide derivatives 26,27 as human carbonic anhydrase IX inhibitors using insilico approach like QSAR followed docking and dynamics identied as new lead compound [28][29][30] with predicted K i = 0.07 nM. Furthermore, we have explored aromatic acid esters in carbonic anhydrase inhibition using CoMFA, CoMSIA and HQSAR 31 approaches.…”