Insight on novel oxindole conjugates adopting different anti-inflammatory investigations and quantitative evaluation.
Future Med Chem
; 16(9): 817-842, 2024.
Article
em En
| MEDLINE
| ID: mdl-38634318
ABSTRACT
Background:
A dual COX/5-LOX strategy was adopted to develop new oxindole derivatives with superior anti-inflammatory activity.Methods:
Three series of oxindoles - esters 4a-p, 6a-l and imines 7a-o - were synthesized and evaluated for their anti-inflammatory and analgesic activities. Molecular docking and predicted pharmacokinetic parameters were done for the most active compounds. A new LC-MS/MS method was developed and validated for the quantification of 4h in rat plasma.Results:
Compounds 4h, 6d, 6f, 6j and 7m revealed % edema inhibition up to 100.00%; also, 4l and 7j showed 100.00% writhing protection. Compound 4h showed dual inhibitory activity with IC50 = 0.0533 and 0.4195 µM for COX-2 and 5-LOX, respectively. Molecular docking rationalized the obtained biological activity. The pharmacokinetic parameters of 4h from rat plasma were obtained.
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Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Araquidonato 5-Lipoxigenase
/
Edema
/
Ciclo-Oxigenase 2
/
Simulação de Acoplamento Molecular
/
Oxindóis
Idioma:
En
Revista:
Future Med Chem
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Egito