A DFT-based quantum theoretic QSAR study of aromatic and heterocyclic sulfonamides as carbonic anhydrase inhibitors against isozyme, CA-II

In this study, DFT/B3LYP level of theory with the 6-31G (d) basis set, was used to calculate a set of molecular descriptors of 30 sulfonamide compounds with carbonic anhydrase inhibitory activity. Quantitative structure–activity relationship (QSAR) models of the biological activity (Ki) of 30 inhibitors of carbonic anhydrase (CA-II) were established using some of the following calculated quantum mechanical descriptors, dipole moment (μ), average polarizability (P), ionization potential (I), electron affinity (A), LUMO energy (ɛLUMO), HOMO energy (ɛHOMO), total energy at 0 K (Te), entropy at 298 K (S), electronegativity (χ), hardness (η), electrophilicity (ω), and differences between HOMO and LUMO energies (ɛH − ɛL). The QSAR models obtained by employing multiple linear regression techniques are aimed at correlating the structures to their reported experimental inhibitory activity values, Ki. Among the models presented in this study, statistically the most significant one is a four-parameter linear equation with correlation coefficient, R2 values of ca. 0.847 and the cross-validated correlation coefficient, R values of ca. 0.775. This study also reconstructed the obtained models using AM1-based calculated descriptors to demonstrate the superiority of DFT over AM1 for quantum calculations of mechanical descriptors. The results are discussed in the light of the main factors that influence the inhibitory activity of carbonic anhydrase (CA-II) isozyme.