Abstract
Three-dimensional quantitative structure-activity relationship (3-D QSAR) was performed using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques in order to understand the carbonic anhydrase inhibition activity. A large number of 25 structurally and functionally diverse series of aromatic heterocyclic sulfonamides carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, such as hCA II were chosen for the study. Based on the alignment generated by docking conformations, a highly predictive comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were developed with q2 value of 0.532 and 0.486 & r2 value of 0.978 and 0.952, respectively. Further, mapping of contours onto the active site validated each other in terms of residues involved with reference to respective contours. This integrated molecular docking based alignment followed by 3D-QSAR studies should provide further insights to support structure based design of human carbonic anhydrase II inhibitors with improved activity profile.
Keywords: 3D-QSAR, CoMFA, CoMSIA, Docking, Carbonic anhydrase inhibitors, hCA II
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