Synthesis and human/bacterial carbonic anhydrase inhibition with a series of sulfonamides incorporating phthalimido moieties.
Bioorg Med Chem
; 25(8): 2524-2529, 2017 04 15.
Article
em En
| MEDLINE
| ID: mdl-28318894
ABSTRACT
A series of sulfonamides was obtained by reacting substituted-2-(1,3-dioxo-1,3-dihydroisobenzofuran-5-carboxamido)benzoic acids with aromatic sulfonamides incorporating primary amino moieties. The new compounds were investigated as inhibitor of four carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I and II, and the α- and ß-class CAs from the pathogenic bacterium Vibrio cholerae, VchCAα and VhcCAß. hCA I was effectively inhibited by the new sulfonamides, with inhibition constants in the range of 4.9-96.0nM. hCA II also showed high affinity for these compounds (KIs of 2.1-22.3nM), whereas the two bacterial enzymes were less effectively inhibited, with KIs of 281-3192nM for VchCAα, and 5.40-9.26µM for VhcCAß. As the physiological function hCA I is poorly understood, and it was recently shown to be involved in the pathogenesis of cerebral malaria and amyotrophic lateral sclerosis, selective and effective inhibitors may be useful as tools or drugs for better understanding this abundant isoform.
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Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Ftalimidas
/
Sulfonamidas
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Vibrio cholerae
/
Inibidores da Anidrase Carbônica
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Ano de publicação:
2017
Tipo de documento:
Article