Lee_2018_Int.J.Biol.Macromol_120_2442

Six diarylheptanoids (1-6) and two flavonoids (7 and 8) derived from Alpinia officinarum were evaluated for their ability to inhibit acetylcholinesterase. Compound 1 showed the highest degree of inhibition, with an IC50 of approximately 2muM, followed by moderate degrees of inhibition by 2, 4 and 7, with IC50 values ranging from 20 to 40muM. The remaining isolated compounds 3, 5, 6 and 8 had IC50 values greater than 50muM. Enzyme kinetic studies showed that the compounds with high or moderate activity were competitive inhibitors, anchored to the active site of acetylcholinesterase. In particular, compounds 1 and 2 were docked at slightly different positions from those occupied by 4 and 7. Furthermore, molecular dynamics studies showed that compound 1 maintained its interactions with residues Thr74 and Phe295 throughout the simulation trajectory. Our findings suggest that compound 1 is a potential therapeutically relevant inhibitor of acetylcholinesterase.