A Series of Thiadiazolyl-Benzenesulfonamides Incorporating an Aromatic Tail as Isoform-Selective, Potent Carbonic Anhydrase II/XII Inhibitors.
ChemMedChem
; 17(10): e202200056, 2022 05 18.
Article
en En
| MEDLINE
| ID: mdl-35266325
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 2.4-31.6â
nM. Besides hCA II, also hCA XII activity was potently inhibited by some of the derivatives (Ki =1.5-88.5â
nM), producing dual inhibitors of both isoforms. Notably, compound 17 was the most potent dual CA II (Ki =3.1â
nM) and XII (Ki =1.5â
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sulfonamidas
/
Inhibidores de Anhidrasa Carbónica
/
Anhidrasa Carbónica II
/
Anhidrasa Carbónica IX
Límite:
Humans
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Turquía