Natural products as sources of acetylcholinesterase inhibitors: Synthesis, biological activities, and molecular docking studies of osthole-based ester derivatives.

Osthole is a natural coumarin compound which isolated from Cusson, has extensive pharmacological activities and could be used as a leading compound for drug research and development. In a continuous effort to develop new acetylcholinesterase inhibitors from natural products, eighteen osthole esters were designed, synthesized, and confirmed by H NMR, C NMR and HRMS. The anti-AChE activity of These derivatives was measured at a concentration of 1.0 mol/mL by Ellman's method, and the result showed that 4m and 4o had moderate inhibitory activities with 68.8% and 62.6%, respectively. Molecular docking study results further revealed AChE interacted optimally with docking poses 4m and 4o. Network pharmacology also predicted that compound 4m could be involved in Ras signaling pathway, which made it a potential therapeutic target of AD.