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Synthesis, α-Glucosidase inhibitory activity and docking studies of Novel Ethyl 1,2,3-triazol-4-ylmethylthio-5,6-diphenylpyridazine-4-carboxylate derivatives

In this work, a novel series of pyridazine-triazole hybrid molecules were prepared and evaluated as inhibitors of rat intestinal α-glucosidase enzyme. Amongst all newly synthesized compounds, 10k showed good inhibition in the series with IC(50) value of 1.7 µM which is 100 folds stronger than positi...

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Detalles Bibliográficos
Autores principales: Firoozpour, Loghman, Moghimi, Setareh, Salarinejad, Somayeh, Toolabi, Mahsa, Rafsanjani, Mahdi, Pakrad, Roya, Salmani, Farzaneh, Shokrolahi, Seyed Mohammad, Sadat Ebrahimi, Seyed Esmail, Karima, Saeed, Foroumadi, Alireza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294378/
https://www.ncbi.nlm.nih.gov/pubmed/37365646
http://dx.doi.org/10.1186/s13065-023-00973-8
Descripción
Sumario:In this work, a novel series of pyridazine-triazole hybrid molecules were prepared and evaluated as inhibitors of rat intestinal α-glucosidase enzyme. Amongst all newly synthesized compounds, 10k showed good inhibition in the series with IC(50) value of 1.7 µM which is 100 folds stronger than positive control, acarbose. The cytotoxicity revealed that this compound is not toxic against normal cell line, HDF. The docking studies showed that triazole ring plays an important role in the binding interactions with the active site. The insertion of compound 10k into the active pocket of α-glucosidase and formation of hydrogen bonds with Leu677 was observed from docking studies. The kinetic studies revealed that this compound has uncompetitive mode of inhibition against α-glucosidase enzyme. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13065-023-00973-8.