Inhibitory effects of serratene-type triterpenoids from Lycopodium complanatum on cholinesterases and β-secretase 1

Abstract Phytochemical investigation of Lycopodium complanatum whole plants led to the isolation of two new serratene-type triterpenoids ( 1 and 2 ) along with eight known triterpenoids ( 3 – 10 ). Their structures were established using 1D and 2D NMR spectroscopic techniques and mass spectrometry. These compounds did not inhibit acetylcholinesterases (AChE) and butyrylcholinesterase (BChE), but did inhibit β-secretase 1 (BACE1). Compounds 1 and 6 showed potent BACE1 inhibition with IC 50 values of 2.79 ± 0.28 and 2.49 ± 0.12 μM, respectively. The kinetic study of BACE1 inhibition revealed that compound 1 showed competitive inhibition, whereas 6 showed mixed-type inhibition. Furthermore, molecular docking results showed that the tested inhibitors 1 and 6 exhibited good binding affinities toward BACE1, with binding energies of −8.8 and −10.3 kcal/mol, respectively.