Propidium-based polyamine ligands as potent inhibitors of acetylcholinesterase and acetylcholinesterase-induced amyloid-beta aggregation.
Heterodimers 4 and 5 were effective inhibitors of acetylcholinesterase (AChE) activity and AChE-induced amyloid-beta (A beta) aggregation. The peculiar biological profile of 4 can be relevant in studying the molecular basis underlying the nonclassical action of AChE and in addressing the question whether AChE inhibitors can affect the neurotoxic cascade leading to Alzheimer's disease. Compound 4 emerged as the most potent heterodimer so far available to inhibit AChE-induced A beta aggregation.
Bolognesi
Maria Laura
ML
Alma Mater Studiorum, University of Bologna, Department of Pharmaceutical Sciences, Via Belmeloro 6, 40126 Bologna, Italy. marialaura.bolognesi@unibo.it
Andrisano
Vincenza
V
Bartolini
Manuela
M
Banzi
Rita
R
Melchiorre
Carlo
C
D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism*; D001671:Biochemistry / Q000379:methods; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D019281:Dimerization; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005470:Fluorometry / Q000379:methods; D006801:Humans; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D008024:Ligands; D011073:Polyamines / Q000737:chemistry*; D011419:Propidium / Q000737:chemistry*; D013329:Structure-Activity Relationship
D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D008024:Ligands; D011073:Polyamines; D011419:Propidium; D000110:Acetylcholinesterase