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

• Published in: BMC chemistry Vol. 17; no. 1; p. 66
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 26-06-2023; Springer Nature B.V; BMC
• Subjects: Cardiovascular disease; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Click reaction; Copper iodide; Diabetes; Docking; Enzymes; Ethanol; Glucose; Glucosidase; Hydrogen bonds; Pharmaceutical sciences; Pharmacy; Pyridizine; Toxicity; Triazole; Triazoles; α-Glucosidase; Triazole; Glucosidase; Click reaction; Diabetes; Copper iodide; Pyridizine; α-Glucosidase
• ISSN: 2661-801X; 2661-801X
• DOI: 10.1186/s13065-023-00973-8

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.