Tran_2025_RSC.Adv_15_16855

Alzheimer's disease is characterized by cholinergic dysfunction and neuroinflammation, with acetylcholinesterase and monoacylglycerol lipase emerging as important therapeutic targets. In this study, a series of novel flavonoid carbamate derivatives were synthesized from chrysin and kaempferol, and their structures were confirmed via NMR and HRMS spectroscopy. The inhibitory activities of these compounds were evaluated against acetylcholinesterase and monoacylglycerol lipase using in vitro enzymatic assays. Among them, C3 and C5 exhibited significant dual inhibition, with IC(50) values of 22.86 microM and 46.65 microM for monoacylglycerol lipase, and 61.78 microM and 89.40 microM for acetylcholinesterase, respectively. Molecular docking studies revealed key binding interactions, while molecular dynamics simulations demonstrated their stability within the active sites of target enzymes. These findings highlight C3 and C5 as promising candidates for further investigation in the development of dual acetylcholinesterase/monoacylglycerol lipase inhibitors for Alzheimer's disease treatment.