Synthesis, computational studies and assessment of in vitro inhibitory activity of umbelliferon-based compounds against tumour-associated carbonic anhydrase isoforms IX and XII.
J Enzyme Inhib Med Chem
; 35(1): 1442-1449, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-32614678
ABSTRACT
Coumarins are widely diffused secondary metabolites possessing a plethora of biological activities. It has been established that coumarins represent a peculiar class of human carbonic anhydrase (hCA) inhibitors having a distinct mechanism of action involving a non-classical binding with amino acid residues paving the entrance of hCA catalytic site. Herein, we report the synthesis of a small series of new coumarin derivatives 7-11, 15, 17 prepared via classical Pechmann condensation starting from resorcinol derivatives and suitable ß-ketoesters. The evaluation of inhibitory activity revealed that these compounds possessed nanomolar affinity and high selectivity towards tumour-associated hCA IX and XII over cytosolic hCA I and hCA II isoforms. To investigate the binding mode of these new coumarin-inspired inhibitors, the most active compounds 10 and 17 were docked within hCA XII catalytic cleft.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Umbeliferonas
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Inibidores da Anidrase Carbônica
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Anidrases Carbônicas
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Simulação de Acoplamento Molecular
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Anidrase Carbônica IX
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Neoplasias
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article