Screening of non-alkaloidal natural compounds as acetylcholinesterase inhibitors.
Acetylcholinesterase (AChE) inhibitors are currently the only approved therapy for the treatment of Alzheimer's disease, only a limited number of drugs are commercially available. A library of non-alkaloidal natural compounds was investigated. To this end, a convenient microtitre plate method for assaying AChE inhibition, which allows a complete kinetic analysis of AChE inhibitors, was developed. Seven active compounds with Ki values in the micromolar range were identified, six of which were xanthones. This is the first report that a promising potential for AChE inhibition exists in such non-nitrogenous natural compounds. Furthermore, four xanthones among these xanthones had already been described as monoamine oxidase (MAO) inhibitors, making then dual AChE/MAO inhibitors of great interest.
Brühlmann
Corinne
C
Laboratoire de Chimie Thérapeutique, Section de Pharmacie Genève-Lausanne, Université de Genève, CH-1211 Genève 4.
Marston
Andrew
A
Hostettmann
Kurt
K
Carrupt
Pierre-Alain
PA
Testa
Bernard
B
D000110:Acetylcholinesterase / Q000378:metabolism; D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000493:pharmacokinetics; D000818:Animals; D001688:Biological Products / Q000737:chemistry* / Q000302:isolation & purification / Q000493:pharmacokinetics; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004524:Eels
D000470:Alkaloids; D001688:Biological Products; D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase