QSARs on human carbonic anhydrase VA and VB inhibitors of some new not yet synthesized, substituted aromatic/heterocyclic sulphonamides as anti-obesity agent

摘要

This paper presents result of quantitative structure–activity relationships (QSAR) study realized with the PRECLAV, omega, brood and MOPAC software. The dependent property is the inhibitory activity against human carbonic anhydrase mitochondrial isoforms VA and VB. The calibration set includes 17 aromatic/heterocyclic sulphonamides incorporating phenacetyl, pyridylacetyl and thienylacetyl tails with three clinically used CA inhibitors namely AZA, TPM and ZNS molecules. The prediction set contains 24 others not yet synthesized substituted aromatic/heterocyclic sulphonamides having unknown observed values of activity. In the presence of prediction set, the predictive quality of QSAR of hCA VA (r2?=?0.9789, F?=?418.115, r2_CV?=?0.9689) and hCA VB (r2?=?0.9768; F?=?379.717; r2_CV?=?0.9637) is large. The obtained models suggest a slightly different inhibition mechanism for the two isoforms. Large percentage, in weight, of CONH molecular fragments seems to be favourable to inhibitory activity of both VA and VB.