jm8b00670_si_005.pdb (152.09 kB)

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

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posted on 18.06.2018, 00:00 by Silvia Salerno, Elisabetta Barresi, Giorgio Amendola, Emanuela Berrino, Ciro Milite, Anna Maria Marini, Federico Da Settimo, Ettore Novellino, Claudiu T. Supuran, Sandro Cosconati, Sabrina Taliani
As a part of our efforts to expand chemical diversity in the carbonic anhydrases inhibitors (CAIs), three small series of polyheterocyclic compounds (46) 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.