Computational deign and QSPR study on carbonic anhydrase mitochondrial isozymes VA inhibitors : As an 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. The calibration set includes 12 2-substituted-1,3,4-thiadiazole-5-sulfamides heterocyclic with two clinically used CA inhibitors namely AZA, and ZNS molecules. The prediction set contains nine others not yet synthesized substituted heterocyclic sulphonamides having unknown observed values of activity. In the presence of prediction set, the predictive quality of QSAR of hCA VA (r(2) = 0.9528, F = 60.5698, r(CV)(2) = 0.9052) is large. The obtained models suggest a slightly different inhibition mechanism for the isoforms. Large percentage, in weight, of C2HN3 molecular fragments seems to be not favorable to inhibitory activity of VA.