Development of selective QSAR models and molecular docking study for inhibitory activity of sulfonamide derivatives against carbonic anhydrase isoforms II and IX

In this study, we presented four linear quantitative structure-activity relationship (QSAR) models, which were developed from calculated molecular descriptors and experimental inhibition constants of 43 sulfonamide compounds measured against carbonic anhydrase (CA) II and IX isoforms. In the first two models, binding affinity of the compounds against CA II and IX isoforms were treated as independent variables, whereas in the remaining two models, taking affinity ratio (RpKi) and differences (ΔpKi) with respect to the two CA isoforms were treated as independent variables. Physically interpretable molecular descriptors involved in the obtained QSAR models allowed us to put forth some structural features, which played a critical role in binding affinity selectivity of the ligands with respect to the two CA isoforms. Furthermore, we applied AUTODOCK protocol for docking simulation of two highly selective ligands, 7c and 8d in binding to CA isoforms. The obtained results demonstrated that interaction of tail moiety of the ligand with Phe131 residue is an important factor for a ligand being highly selective for CA II binding.