Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α-amylase, and α-glucosidase: synthesis, molecular docking, and ADMET studies.
J Enzyme Inhib Med Chem
; 39(1): 2367128, 2024 Dec.
Article
em En
| MEDLINE
| ID: mdl-38913598
ABSTRACT
Inhibition of α-glucosidase and α-amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat diabetes. Indeno[1,2-b] quinoxalines-carrying thiazole hybrids 1-17 were created and described using NMR. All analogues were tested for hypoglycaemic effect against STZ-induced diabetes in mice. Compounds 4, 6, 8, and 16 were the most potent among the synthesised analogues. These hybrids were examined for their effects on plasma insulin, urea, creatinine, GSH, MDA, ALT, AST, and total cholesterol. Moreover, these compounds were tested against α-glucosidase and α-amylase enzymes in vitro. The four hybrids 4, 6, 8, and 16 represented moderate to potent activity with IC50 values 0.982 ± 0.04, to 10.19 ± 0.21 for α-glucosidase inhibition and 17.58 ± 0.74 to 121.6 ± 5.14 µM for α-amylase inhibition when compared to the standard medication acarbose with IC50=0.316 ± 0.02 µM for α-glucosidase inhibition and 31.56 ± 1.33 µM for α-amylase inhibition. Docking studies as well as in silico ADMT were done.
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Base de dados:
MEDLINE
Assunto principal:
Quinoxalinas
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Tiazóis
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Relação Dose-Resposta a Droga
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Alfa-Amilases
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Alfa-Glucosidases
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Simulação de Acoplamento Molecular
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Inibidores de Glicosídeo Hidrolases
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Hipoglicemiantes
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article