Quinazolinone-dihydropyrano[3,2-b]pyran hybrids as new α-glucosidase inhibitors: Design, synthesis, enzymatic inhibition, docking study and prediction of pharmacokinetic.
Bioorg Chem
; 109: 104703, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33609917
ABSTRACT
A series of new quinazolinone-dihydropyrano[3,2-b]pyran derivatives 10A-L were synthesized by simple chemical reactions and were investigated for inhibitory activities against α-glucosidase and α-amylase. New synthesized compounds showed high α-glucosidase inhibition effects in comparison to the standard drug acarbose and were inactive against α-amylase. Among them, the most potent compound was compound 10L (IC50 value = 40.1 ± 0.6 µM) with inhibitory activity around 18.75-fold more than acarboase (IC50 value = 750.0 ± 12.5 µM). This compound was a competitive inhibitor into α-glucosidase. Our obtained experimental results were confirmed by docking studies. Furthermore, the cytotoxicity of the most potent compounds 10L, 10G, and 10N against normal fibroblast cells and in silico druglikeness, ADME, and toxicity prediction of these compounds were also evaluated.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piranos
/
Alfa-Glucosidases
/
Simulação de Acoplamento Molecular
/
Inibidores de Glicosídeo Hidrolases
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Irã