4‑Substituted Benzenesulfonamides Incorporating Bi/Tricyclic Moieties Act as Potent and Isoform-Selective Carbonic Anhydrase II/IX Inhibitors

As a part of our efforts to expand
chemical diversity in the carbonic
anhydrases inhibitors (CAIs), three small series of polyheterocyclic
compounds (4–6) featuring the primary
benzenesulfonamide moiety linked to bi/tricyclic scaffolds were investigated.
Highly effective inhibitors against the target tumor-associated hCA
IX (low nanomolar/subnanomolar potency levels) showing significant
functional selectivity profile toward hCA I, II, and IV isozymes were
identified. Molecular docking studies clarified the reasons behind
the activity and selectivity of the new compounds.