Anticholinesterase activity of plastoquinones from Sargassum sagamianum: lead compounds for Alzheimer's disease therapy.
During the search for anticholinesterase compounds from marine organisms, two known plastoquinones, sargaquinoic acid (1) and sargachromenol (2), were isolated from Sargassum sagamianum. Both compounds showed moderate acetylcholinesterase (AChE) inhibitory activity in a micromole range (IC(50) 23.2 and 32.7 microm, respectively). However, for butyrylcholinesterase (BuChE), a new target for the treatment of Alzheimer's disease (AD), compound 1 showed particularly potent inhibitory activity (IC(50) 26 nm), which is 1000-fold greater than for AChE. Hence, sargaquinoic acid represents an effective and selective inhibitor of BuChE with a potency similar to or greater than the anticholinesterases in current clinical use, making it an interesting potential drug candidate for AD.
Choi
Byoung Wook
BW
Laboratory of Aging and Degenerative Disease and Department of Applied Chemistry, Hanbat National University, 16-1 Dukmyung-dong, Yuseong-gu, Daejeon, Korea.
Ryu
Geonseek
G
Park
Soo Hee
SH
Kim
Eun Sook
ES
Shin
Jongheon
J
Roh
Seok Seon
SS
Shin
Hyeon Cheol
HC
Lee
Bong Ho
BH
D000110:Acetylcholinesterase / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000188:drug therapy*; D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016227:Benzoquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008517:Phytotherapy; D044647:Sargassum / Q000737:chemistry*
D000475:Alkenes; D001578:Benzopyrans; D016227:Benzoquinones; D002800:Cholinesterase Inhibitors; C503204:sargachromenol; C477718:sargaquinoic acid; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase