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 K-i 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 (K-i=1.5-88.5 nM), producing dual inhibitors of both isoforms. Notably, compound 17 was the most potent dual CA II (K-i=3.1 nM) and XII (K-i=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.

A Series of Thiadiazolyl-Benzenesulfonamides Incorporating an Aromatic Tail as Isoform-Selective, Potent Carbonic Anhydrase II/XII Inhibitors / Banoglu, Erden; Ercanlı, Taner; Gür Maz, Tuğçe; Vullo, Daniela; Bonardi, Alessandro; Gratteri, Paola; Supuran, Claudiu T. - In: CHEMMEDCHEM. - ISSN 1860-7179. - ELETTRONICO. - 17:(2022), pp. 0-0. [10.1002/cmdc.202200056]

A Series of Thiadiazolyl-Benzenesulfonamides Incorporating an Aromatic Tail as Isoform-Selective, Potent Carbonic Anhydrase II/XII Inhibitors

Vullo, Daniela;Bonardi, Alessandro;Gratteri, Paola;Supuran, Claudiu T
2022

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 K-i 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 (K-i=1.5-88.5 nM), producing dual inhibitors of both isoforms. Notably, compound 17 was the most potent dual CA II (K-i=3.1 nM) and XII (K-i=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.
2022
17
0
0
Goal 3: Good health and well-being
Banoglu, Erden; Ercanlı, Taner; Gür Maz, Tuğçe; Vullo, Daniela; Bonardi, Alessandro; Gratteri, Paola; Supuran, Claudiu T
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1307440
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