Structural optimization of new class of selective carbonic anhydrase inhibitors: QSAR approach

Abstract

Quantitative structure activity relationship studies have been conducted on a series (24 compounds) of sulfonamide derivatives with selective carbonic anhydrase inhibitory activity using ChemOffice v.8.0 software. The best predictions have been obtained for hCA-II enzyme inhibition activity (Q²= 0.552, r²= 0.724) and with hCA-VII enzyme inhibition activity (Q²= 0.501, r²= 0.704). Both equations are validated by a test set of compounds and give satisfactory predictive r² values of 0.434 and 0.608, respectively. The equations selected emphasized the importance of LogP (octanol/water partition coefficient), Highest Occupied Molecular Orbital (HOMO) and Radius of gyration (Rgy) on biological activity i.e.; hydrophobic groups, presence of electron donating groups, size and shape of molecule might be influencing the selective carbonic anhydrase inhibitory activity.