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

•Two new and eight known serratene-type triterpenoids were isolated from Lycopodium complanatum.•Isolated compounds exerted as inhibition of cholinesterase (ChEs) and BACE1.•BACE1 inhibitors (1 and 6) have beneficial therapeutic potential for AD.

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 IC50 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.

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