ABSTRACT
Two new isoquinoline alkaloids, named fumaranine (2) and fumarostrejdine (10), along with 18 known alkaloids were isolated from aerial parts of Fumaria officinalis. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses and by comparison with literature data. The absolute configuration of the new compound 2 was determined by comparing its circular dichroism spectra with those of known analogs. Compounds isolated in sufficient amounts were evaluated for their acetylcholinesterase, butyrylcholinesterase, prolyl oligopeptidase (POP), and glycogen synthase kinase-3ß inhibitory activities. Parfumidine (8) and sinactine (15) exhibited potent POP inhibition activities (IC50 99±5 and 53±2â µM, resp.).
Subject(s)
Alkaloids/pharmacology , Alzheimer Disease/drug therapy , Enzyme Inhibitors/pharmacology , Fumaria/chemistry , Isoquinolines/pharmacology , Acetylcholinesterase/metabolism , Alkaloids/chemistry , Alkaloids/isolation & purification , Alzheimer Disease/enzymology , Butyrylcholinesterase/metabolism , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Glycogen Synthase Kinase 3/antagonists & inhibitors , Glycogen Synthase Kinase 3/metabolism , Glycogen Synthase Kinase 3 beta , Humans , Isoquinolines/chemistry , Isoquinolines/isolation & purification , Molecular Structure , Prolyl Oligopeptidases , Serine Endopeptidases/metabolism , Structure-Activity RelationshipABSTRACT
The deposit of two proteins in the brain characterizes Alzheimer's disease: deposits of beta-amyloid protein to form senile plaques and tau protein in neurofibrillary tangles. This review discusses transgenic animals overexpressing normal or mutated tau protein as well as kinases involved in tau hyperphosphorylation. These animals hold a great potential as tools to test the effects of forthcoming therapeutical agents for Alzheimer's disease.
