Tailored Tetrasubstituted Imidazole Carrying the Benzenesulfonamide Fragments as Selective Human Carbonic Anhydrase IX/XII Inhibitors.
ChemMedChem
; 19(10): e202400004, 2024 May 17.
Article
em En
| MEDLINE
| ID: mdl-38356418
ABSTRACT
A new series of tetrasubstituted imidazole carrying sulfonamide as zinc-anchoring group has been designed. The structures of the synthesized derivatives 5 a-l have been confirmed by spectroscopic analysis. These compounds incorporate an ethylenic spacer between the benzenesulfonamide and the rest of the trisubstituted imidazole moiety and were tested as inhibitors of carbonic anhydrases and for in-vitro cytotoxicity. Most of them act as effective inhibitors of the tumor-linked CA isoforms IX and XII, in nanomolar range. Also, different compounds have shown selectivity in comparable with the standard acetazolamide. Our IBS 5 d, 5 g, and 5 l (with Ki 10.1, 19.4, 19.8â
nM against hCA IX and 47, 45, 20â
nM against hCA IX) showed the best inhibitory profile. In-vitro screening of all derivatives against a full sixty-cell-lined from NCI at a single dose of 10â
µM offered growth inhibition of up to 45 %. Compoundâ
5 b has been identified with the most potent cytotoxic activity and broad spectrum. Docking studies have also been implemented and were also in accordance with the biological outcomes. Our SAR analysis has interestingly proposed efficient tumor-related hCAs IX/XII suppression.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores da Anidrase Carbônica
/
Anidrases Carbônicas
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Anidrase Carbônica IX
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Benzenossulfonamidas
/
Imidazóis
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article