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 µM, 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.
School of Pharmacy, Guiyang Medical University, Guiyang, China.
Hai-Tao
HT
Xiao
Jiao
J
Peng
Yan
Y
Liang
Jie
J
Yang
Xue
X
Bai
Xiao-Yan
XY
Hao
Fu-Mei
FM
Yang
Qian-Yun
QY
Sun
D000110:Acetylcholinesterase / Q000187:drug effects*; D001681:Biological Assay; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D031311:Corydalis / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization
D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase