Synthesis of novel chromenones linked to 1,2,3-triazole ring system: Investigation of biological activities against Alzheimer’s disease

Novel chromenones linked to 1,2,3-triazole ring system were synthesized and evaluated for their anti-ChE activity. Among them, N-((1-(2-chlorobenzyl)-1H-1,2,3-triazol-5-yl)methyl)-8-methoxy-2-oxo-2H-chromene-3-carboxamide (6m) showed good anti-acetylcholinesterase activity (IC50=15.42μM). [Display omitted] •Novel chromenones linked to 1,2,3-triazole ring system were synthesized and evaluated for their anti-ChE activity.•Among them, N-((1-(2-chlorobenzyl)-1H-1,2,3-triazol-5-yl)methyl)-8-methoxy-2-oxo-2H-chromene-3-carboxamide (6m) showed good anti-acetylcholinesterase activity (IC50=15.42μM).•Compound 6m also showed neuroprotective effect against H2O2-induced cell death in PC12 neurons.•Compound 6m showed no inhibitory activity toward beta-secretase (BACE1). In this work, novel chromenones linked to 1,2,3-triazole ring system were synthesized and evaluated for their anti-ChE activity. Among them, N-((1-(2-chlorobenzyl)-1H-1,2,3-triazol-5-yl)methyl)-8-methoxy-2-oxo-2H-chromene-3-carboxamide (6m) showed good anti-acetylcholinesterase activity (IC50=15.42μM). Also, compound 6m demonstrated neuroprotective effect against H2O2-induced cell death in PC12 neurons, however, it showed no beta-secretase (BACE1) inhibitory activity. Docking and kinetic studies separately confirmed dual binding activity of compound 6m since it targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE.