Investigation on Hydrazonobenzenesulfonamides as Human Carbonic Anhydrase I, II, IX and XII Inhibitors
Davide Moi,
Serena Vittorio,
Andrea Angeli,
Gianfranco Balboni,
Claudiu T. Supuran,
Valentina Onnis
Affiliations
Davide Moi
Department of Life and Environmental Sciences, University of Cagliari, University Campus, S.P. 8 CA, 09042 Monserrato, Italy
Serena Vittorio
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano,Via Mangiagalli 25, 20133 Milano, Italy
Andrea Angeli
Laboratorio di Chimica Bioinorganica, Polo Scientifico Neurofarba Department, Università Degli Studi di Firenze, Room 188, Via della Lastruccia 3, Sesto Fiorentino, 50019 Florence, Italy
Gianfranco Balboni
Department of Life and Environmental Sciences, University of Cagliari, University Campus, S.P. 8 CA, 09042 Monserrato, Italy
Claudiu T. Supuran
Laboratorio di Chimica Bioinorganica, Polo Scientifico Neurofarba Department, Università Degli Studi di Firenze, Room 188, Via della Lastruccia 3, Sesto Fiorentino, 50019 Florence, Italy
Valentina Onnis
Department of Life and Environmental Sciences, University of Cagliari, University Campus, S.P. 8 CA, 09042 Monserrato, Italy
A small series of hydrazonobenzenesulfonamides was designed, synthesized and studied for their human carbonic anhydrase (hCA) inhibitory activity. The synthesized compounds were evaluated against hCA I, II, IX and XII isoforms using acetazolamide (AAZ) as the standard inhibitor. Various hydrazonosulfonamide derivatives showed inhibitory activity at low nanomolar levels with selectivity against the cytosolic hCA II isoform, as well as the transmembrane, tumor-associated enzymes hCA IX and XII. The most potent and selective hydrazones 8, 9, 10, 11, 19 and 24 were docked into isoforms I, II, IX and XII to better understand their activity and selectivity for the different CA isoforms.
