New insights into the acetylcholinesterase inhibitory activity of Lycopodium clavatum

Looking for acetylcholinesterase (AChE) inhibiting compounds within the plant kingdom, we came across the triterpene α-onocerin, which has recently been described as the active principle (IC₅₀ of 5.2 μM) of Lycopodium clavatum L. In order to discover related terpenoid structures with similar AChE inhibitory activity, we investigated the roots of Ononis spinosa L. using Ellman's reagent in a microplate assay. No inhibitory effect could be measured, not even with the isolated α-onocerin (1), which is in contrast to previous findings. Bioassay-guided fractionation of L clavatum resulted in the isolation of lyclavatol (2), showing a weak, but dose-dependent inhibitory effect on AChE. ¹H- and ¹³C NMR shift assignments for 1 and 2 are presented and discussed.