ARISUGACINS, SELECTIVE ACETYLCHOLINESTERASE INHIBITORS OF MICROBIAL ORIGIN

Synthetic inhibitors of acetylcholinesterase (AChE) recently have attr acted particular attention for treatment of Alzheimer's disease. By sy stematic screening of microbial metabolites, we were able to discover the new AChE inhibitors, named arisugacins A and B, from the culture b roth of Penicillium sp. FO-4259. The structures of arisugacins are mem bers of the meroterpenoid compounds. Arisugacin A is a potent and high ly selective inhibitor of AChE but does not inhibit butyrylcholinester ase in vitro. Arisugacin A is a good candidate as an excellent potenti al drug for treatment of Alzheimer's disease. Also reviewed is the cur rent status of development of antidementia drugs. (C) 1997 Elsevier Sc ience Inc.