Acetylcholinesterase inhibitors from Stephania venosa tuber.
Acetylcholinesterase (AChE) inhibitors have lately gained interest as potential drugs in the treatment of Alzheimer's disease. Three AChE inhibitors were isolated from tubers of a Thai medicinal plant, Stephania venosa (Bl) Spreng. They were identified as quaternary protoberberine alkaloids, stepharanine, cyclanoline and N-methyl stepholidine. They expressed inhibitory activity on AChE with IC50 values (concentration that caused 50% inhibition of activity) of 14.10 +/- 0.81, 9.23 +/- 3.47 and 31.30 +/- 3.67 microM, respectively. The AChE inhibitory activity of these compounds was compared with those of the related compounds, palmatine, jatrorrhizine and berberine, as well as tertiary protoberberine alkaloids isolated from the same plant, stepholidine and corydalmine. The results suggest that the positive charge at the nitrogen of the tetrahydroisoquinoline portion, steric substitution at the nitrogen, planarity of the molecule or substitutions at C-2, -3, -9, and -10 affect the AChE inhibitory activity of protoberberine alkaloids.
Ingkaninan
Kornkanok
K
Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand. ingkaninan@yahoo.com
Phengpa
Preeda
P
Yuenyongsawad
Supreeya
S
Khorana
Nantaka
N
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D001599:Berberine / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology; D001600:Berberine Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D035281:Plant Tubers / Q000737:chemistry; D031607:Stephania / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013785:Thailand
D001600:Berberine Alkaloids; D002800:Cholinesterase Inhibitors; D001599:Berberine; C060801:cyclanoline; C009090:protoberberine; D000110:Acetylcholinesterase