Carbonic anhydrases (CA) are a group of zinc-containing enzymes involved in many physiological processes with their role in the maintenance of the equilibrium between bicarbonate and CO₂ levels. Human carbonic anhydrases (hCA) are recognized as important drug targets due to their major implication in the development of diseases including cancer.

Sulfanilamide derivatives were widely studied and showed remarkable efficiency in inhibiting carbonic anhydrases; with the presence of SO₂NH₂ in their structure. Therefore, sulfonamide moiety is considered as the leading scaffold in the search for new hCA inhibitors.

Moreover, the introduction of an enaminone to sulfonamide-based CA inhibitors showed an enhancement of the inhibitory activity.

In this context, we were interested in the in silico investigation of benzenesulfonamide derivatives containing β-enaminone that were synthesized from dicarbonyl compounds and sulfanilamide under microwave irradiation. The in silico assessment includes a molecular docking simulation against hCA II (PDB: 2AW1). The docked ligands showed good docking score values (-8.099 and -7.053 kcal.mol^-1), which indicates a good stability of the studied compounds within the active site. Further, significant interactions with the residues of the active site was observed including a metal coordination with the Zn 262, an H-bond with Thr199, and a pi-pi stacking with the side chain of His94, which are considered as the key interactions for a CA inhibition.

A complementary in silico study that involves an ADMET prediction was performed to learn more about the pharmacokinetics properties and the toxicity of the products in order to comprehend their ability to become drug-candidates.