Acetylcholinesterase inhibitors from Corydalis yanhusuo

In a bioassay-guided search for acetylcholinesterase (AChE) inhibitors from Chinese natural resources, eight isoquinoline alkaloids, tetrahydropalmatine (1), corydaline (2), protopine (3), berberine (4), palmatine (5), jatrorrhizine (6), coptisine (7) and dehydrocorydaline (8), were isolated from the methanolic extract of the tubers of Corydalis yanhusuo. Structures of these compounds were identified by spectroscopic techniques. Compounds 4-8 inhibited AChE activity in a dose-dependent manner, and the IC50 values were 0.47 +/- 0.01, 0.74 +/- 0.06, 2.08 +/- 0.09, 1.01 +/- 0.03 and 0.62 +/- 0.05 mu M, respectively. Structure-activity relationship analysis suggested that aromatisation at ring C, as well as substitutions at C-2, C-3, C-9, C-10 and C-13 affect the AChE activity of protoberberine alkaloids.