| Affiliation: | 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Taç Sok. No:3 Yenimahalle, 06560 Ankara, Turkey;2. Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via Ugo Schiff 6, 50019 Sesto Fiorentino Firenze, Italy;3. Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via Ugo Schiff 6, 50019 Sesto Fiorentino Firenze, Italy Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019 Sesto Fiorentino Firenze, Italy;4. Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019 Sesto Fiorentino Firenze, Italy |
| Abstract: | We describe the synthesis of a series of thiadiazolyl-benzenesulfonamide derivatives carrying an aromatic tail linked by an amide linker ( 12–34 ), as human carbonic anhydrase (hCA) inhibitors. These thiadiazol derivatives were evaluated against four physiologically relevant CA isoforms (hCA I, II, IX, and XII), and demonstrated intriguing inhibitory activity against CA II with Ki values in the range of 2.4–31.6 nM. Besides hCA II, also hCA XII activity was potently inhibited by some of the derivatives (Ki=1.5–88.5 nM), producing dual inhibitors of both isoforms. Notably, compound 17 was the most potent dual CA II (Ki=3.1 nM) and XII (Ki=1.5 nM) inhibitor with a significant selectivity ratio over CA I and IX isoforms. In conclusion, although all compounds exhibited preferential activity towards hCA II, the nature of the substituents at the tail part of the main scaffold influenced the activity and selectivity toward other isoforms. |
