Molecular Docking Studies and In-Vitro Cholinesterase Enzyme Inhibitory Activities of Chemical Constituents of Calophyllum Gracilentum

Calophyllum species is well known due to its abundance of potentially beneficial phytochemicals, such as xanthones, coumarins, and others. However, Calophyllum gracilentum is an understudied species with very limited information. Medicinal plants have been proven to have therapeutic potential in the management of neurological disorders associated with AChE dysregulation, but there has been little investigation on Calophyllum plants for this purpose. Herein, we report on the isolation of twelve known oxygenated xanthones (1-12), three chromanone acids (13-15), and triterpenoids (16-18), respectively from the stem bark of the Calophyllum gracilentum. The evaluation of acetylcholinesterase (AChE) inhibitory activity showed that all of the extracts and xanthones (1-4, 6-8, 10, 12) tested have potential acetylcholinesterase (AChE) inhibitory activity. Compounds (3) and (12) are prospective AChE inhibitors with IC50 values of 0.513 and 1.297 µg/mL. The molecular docking analysis demonstrated the two compounds bind well to the active site of Torpedo californica acetylcholinesterase (TcAChE) through π-π stacking, hydrogen bonding, and pi-donor hydrogen bond from the xanthone ring, besides p-alkyl and pi-sigma interactions from the substituent group with the binding energy of -11.1 kcal/mol for (3) and binding energy of -10.4 kcal/mol for (12).