Lycodine-type alkaloids from Lycopodiastrum casuarinoides and their acetylcholinesterase inhibitory activity

Five previously undescribed lycodine-type alkaloids, named huperzine Y (1), 8,15-epoxy-N-demethylhuperzinine (2), 7-hydroxyl-huperzinine (3), huperzine Z (4), and huperzine D N-oxide (5), were isolated from the aerial parts and roots of Lycopodiastrum casuarinoides (Lycopodiaceae), along with ten known analogues. The structures of the new compounds were elucidated by means of spectroscopic technique (IR, UV, MS and NMR). The absolute configurations of the new compounds were established on the basis of comparison of their experimental and TD-DFT (time-dependent density functional theory) calculated ECD spectra. Moreover, all the isolates were evaluated for acetylcholinesterase (AChE) inhibitory activity. Only huperzine C showed moderate activity, with an IC50 value of 0.525 +/- 0.140 mu M, which was comparable with the positive control, huperzine A (IC50 = 0.143 +/- 0.029 mu M).