Sulfonate and sulfamate derivatives possessing benzofuran or benzothiophene nucleus as potent carbonic anhydrase II/IX/XII inhibitors.
Bioorg Med Chem
; 27(17): 3889-3901, 2019 09 01.
Article
em En
| MEDLINE
| ID: mdl-31345748
ABSTRACT
In the current work, we report the discovery of new sulfonate and sulfamate derivatives of benzofuran- and benzothiophene as potent inhibitors of human carbonic anhydrases (hCAs) II, IX and XII. A set of derivatives, 1a-t, having different substituents on the fused benzofuran and benzothiophene rings (Râ¯=â¯alkyl, cyclohexyl, aryl, NH2, NHMe, or NMe2) was designed and synthesized. Most of the derivatives exhibited higher potency than acetazolamide as inhibitors of the purified hCAII, IX and XII isoforms. The most potent inhibitors for hCAII, hCAIX and hCAXII were 1g, 1b and 1d with an IC50⯱â¯SEM values of 0.14⯱â¯0.03, 0.13⯱â¯0.03 and 0.17⯱â¯0.06⯵M, respectively. In addition, compounds 1d and 1n exerted preferential inhibitory effect against hCAXII isozyme with good potencies. Some selected compounds were docked within the active pocket of these isozymes and binding of the molecules revealed that sulfonate and sulfamate rings were located towards the active cavity and compounds coordinated to zinc ions.
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Base de dados:
MEDLINE
Assunto principal:
Ácidos Sulfônicos
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Tiofenos
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Benzofuranos
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Inibidores da Anidrase Carbônica
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Anidrases Carbônicas
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article