Design, synthesis, and biological evaluation of (thio)urea derivatives as potent Escherichia coli ß-glucuronidase inhibitors.
J Enzyme Inhib Med Chem
; 39(1): 2387415, 2024 Dec.
Article
em En
| MEDLINE
| ID: mdl-39140677
ABSTRACT
EcGUS has drawn considerable attention for its role as a target in alleviating serious GIAEs. In this study, a series of 72 (thio)urea derivatives were designed, synthesised, and biologically assayed. The bioassay results revealed that E-9 (IC50 = 2.68 µM) exhibited a promising inhibitory effect on EcGUS, surpassing EcGUS inhibitor D-saccharic acid-1,4-lactone (DSL, IC50 = 45.8 µM). Additionally, the inhibitory kinetic study indicated that E-9 (Ki = 1.64 µM) acted as an uncompetitive inhibitor against EcGUS. The structure-activity relationship revealed that introducing an electron-withdrawing group into the benzene ring at the para-position is beneficial for enhancing inhibitory activity against EcGUS. Furthermore, molecular docking analysis indicated that E-9 has a strong affinity to EcGUS by forming interactions with residues Asp 163, Tyr 472, and Glu 504. Overall, these results suggested that E-9 could be a potent EcGUS inhibitor, providing valuable insights and guidelines for the development of future inhibitors targeting EcGUS.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
/
Relação Dose-Resposta a Droga
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Inibidores Enzimáticos
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Escherichia coli
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Glucuronidase
Idioma:
En
Revista:
J Enzyme Inhib Med Chem
/
J. enzyme inhib. med. chem
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Journal of enzyme inhibition & medicinal chemistry
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China