ABSTRACT

Carbonic Anhydrase (CA) enzyme catalyse the inter-conversion of carbon dioxide and water to bicarbonate and proton, thus it is involved in crucial physiological processes in the body while the overexpression of this enzyme leads to various disorders. Among various human CA isozymes, CA XII isoform is mostly expressed in cancer cells. Because QSAR analysis is one of the most frequently used modelling technique, here 2D and 3D-QSAR studies were carried out on previously synthesized series of 3-phenyl-5-aryl-N-(4-sulfamoylphenyl)-4,5-dihydro-1H-pyrazole-1- carboxamide derivatives as carbonic anhydrase XII inhibitors using software VLife MDS version 4.6. From the various developed 2D and 3D-QSAR models, the best model with good predictive capability of r2 and pred r2 and correlative coefficient (q2 ) were selected. In 3D-QSAR technique, models were developed by using various methods of k-nearest neighbour molecular field analysis (kNN-MFA). 2D-QSAR model depicts contribution of descriptors like T_N_Cl_7, chi6chain and T_2_F_5 for inhibition of CA XII isozyme activity. The results of 3D-QSAR models provides a direct view of factors expressed in terms of molecular field (electrostatic and steric) influencing the activity of CA XII isozyme on the derivatives. The information provided by the 2D and 3D-QSAR studies may lead to better understanding of the structural requirement for carbonic anhydrase XII inhibitors. Keywords: 2D-QSAR, 3D-QSAR, hCA XII
Publication date: 01/12/2021

https://ijbpas.com/pdf/2021/December/MS_IJBPAS_2021_DEC_SPCL_2001.pdf

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https://doi.org/10.31032/IJBPAS/2021/10.12.2001