Virtual screening of the potential hCA XII inhibitors based on the pharmacophore modelling, molecular docking, MMGBSA and molecular dynamics simulations studies

Human carbonic anhydrase XII (hCA XII) has gained therapeutic value in the field of medicinal chemistry as a pharmacological target and biomarker for different types of cancer. Despite the fact that interaction features of hCAs inhibitors with the catalytic site of the enzyme are well described, lack in the selectivity of the traditional hCA inhibitors is an urgent issue. This study was devoted to the identification of novel potential hCA XII inhibitors using comprehensive set of computational approaches, including generation of structure-and ligand-based pharmacophore models, molecular docking, MMGBSA calculations and molecular dynamics simulations. As the results of the study multiple potential hCA inhibitors were identified. Along with the identified derivatives of the classical hCA inhibitors (have sulfonamide motifs), several compounds with alternative chemical scaffolds, that can be considered and further investigated as potential non-classical hCA XII inhibitors, were identified.