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.
Xiao
Hai-Tao
HT
School of Pharmacy, Guiyang Medical University, Guiyang, China.
Peng
Jiao
J
Liang
Yan
Y
Yang
Jie
J
Bai
Xue
X
Hao
Xiao-Yan
XY
Yang
Fu-Mei
FM
Sun
Qian-Yun
QY
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