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

BMC Chemistry

Research

Farzaneh Salmani¹  Seyed Mohammad Shokrolahi¹  Roya Pakrad¹  Saeed Karima¹  Loghman Firoozpour²  Seyed Esmail Sadat Ebrahimi²  Somayeh Salarinejad²  Mahdi Rafsanjani²  Alireza Foroumadi³  Mahsa Toolabi⁴  Setareh Moghimi⁵ 

[1] Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran;Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran;Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran;Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran;

关键词: Pyridizine;    α;    Click reaction;    Triazole;    Copper iodide;    Diabetes;   

DOI  :  10.1186/s13065-023-00973-8

 received in 2022-10-24, accepted in 2023-05-30,  发布年份 2023

来源: Springer

【 摘 要 】

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 IC50 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 10kinto 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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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Fig. 2

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