Title: Galanthamine as bis-functional ligand for the acetylcholinesterase Luttmann E, Linnemann E, Fels G Ref: J Mol Model (Online), 8:208, 2002 : PubMed
Acetylcholinesterase plays a key role in the development of Alzheimer's disease as this enzyme is responsible for cleavage of the neurotransmitter acetylcholine, and, according to recent investigations, also promotes aggregation of beta-amyloid peptides, which causes plaque formation in synaptic areas. We have performed a molecular modeling study to investigate bis-galanthamine derivatives connected by a methylene spacer of varying length as dual acting acetylcholinesterase ligands. Our results suggest that such ligands indeed can interact simultaneously with both biological functions of the enzyme and should therefore serve as the basis for a further development of bis-functional Alzheimer drugs.
        
Title: Potent acetylcholinesterase inhibitors: design, synthesis and structure-activity relationships of alkylene linked bis-galanthamine and galanthamine-galanthaminium salts Guillou C, Mary A, Renko DZ, Gras E, Thal C Ref: Bioorganic & Medicinal Chemistry Lett, 10:637, 2000 : PubMed
The syntheses, the anticholinesterase activities and structure-activity relationships of homodimeric (3a-c) and heterodimeric (6a-c) alkylene linked bis-galanthamine are reported. Compounds 6b-c were found to be more potent than galanthamine and tacrine in inhibiting AChE.