Synthesis and evaluation of coumarin/1,2,4-oxadiazole hybrids as selective BChE inhibitors with neuroprotective activity.

A series of new coumarin/1,2,4-oxadiazole hybrids were synthesized and evaluated for cholinesterase inhibitory and neuroprotective activities. Among them, enantiomers 5u and 5v showed potent hBChE inhibitory activity with IC50 values of 8.17 and 9.56 μM, respectively, and also exhibited good selectivity for hBChE over hAChE by 9.49- and 7.58-fold, respectively. In addition, both compounds could protect SH-SY5Y cells against Aβ25-35 -induced neurotoxicity. The preliminary bioassay results provided a new chemotype for multifunctional anti-Alzheimer's disease agents and continuing investigation into compounds 5u and 5v is warranted.