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 (IC50 23.2 and 32.7 mu m, respectively). However, for butyrylcholinesterase (BuChE), a new target for the treatment of Alzheimer's disease (AD), compound 1 showed particularly potent inhibitory activity (IC50 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. Copyright (c) 2007 John Wiley & Sons, Ltd.