Design, synthesis, SAR, and biological evaluation of saccharin-based hybrids as carbonic anhydrase inhibitors.
Arch Pharm (Weinheim)
; 355(8): e2200019, 2022 Aug.
Article
em En
| MEDLINE
| ID: mdl-35484599
ABSTRACT
Saccharin is a cyclic secondary sulfonamide, which is a selective inhibitor of the tumor-associated carbonic anhydrase (CA; EC 4.2.1.1) enzymes CA IX and CA XII compared to many primary sulfonamides. In this study, new saccharin-1,2,3-triazole and saccharin-1,2,4-oxadiazole hybrids were synthesized. All the newly synthesized molecules were screened for their CA-inhibitory activity against four important human CA (hCA) isoforms hCA I, hCA II, hCA IX, and hCA XII. Compounds 8a and 8f emerged as potent hCA II inhibitors (Ki = 3 µM). Compounds 6d, 6e and 7a, 7b were highly selective against hCA IX (6d, 6e) and hCA II (7a, 7b), with moderate inhibitory activity. The activity of these compounds was further confirmed by performing in silico docking studies against hCA II and hCA IX.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores da Anidrase Carbônica
/
Anidrases Carbônicas
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article