Synthesis and α‐Glucosidase Inhibitory Activity of Ethyl 3‐coumarincarboxylate‐1,2,3‐triazole‐ N ‐phenylacetamide Derivatives
Hejran Khazal Dahils Alnofli, Shiva Khalil‐Moghaddam, Aida Iraji, Hanieh Jafary, Maryam Mohammadi‐Khanaposhtani, Fatemeh Eftekharian, Somayeh Mojtabavi, Mohammad MahdaviABSTRACT
This study employs a molecular hybridization strategy to design a novel series of α‐glucosidase inhibitors with ethyl 3‐coumarincarboxylate‐1,2,3‐triazole‐ N ‐phenylacetamide scaffold. For this purpose, 14 derivatives (compounds 8a‐n ) with various substituents in the N ‐phenylacetamide moiety were synthesized. According to the in vitro α‐glucosidase inhibitory assay, all the synthesized compounds, except compounds 8g (3‐chloro derivative) and 8l (3‐nitro derivative), were more potent than acarbose as a standard inhibitor. The IC 50 values for the potent compounds ranged from 30.8 to 393.1 µM, whereas the IC 50 value of acarbose was 750.0 µM. The most potent compound was ethyl 2‐oxo‐7‐((1‐(2‐oxo‐2‐(phenylamino)ethyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)‐2H‐chromene‐3‐carboxylate ( 8a ), which is a competitive α‐glucosidase inhibitor. Furthermore, in silico enzyme–ligand interaction assays demonstrated that compound 8a interacted with key residues in the active site of α‐glucosidase, forming a stable complex with the enzyme.