Design and activity of cationic fullerene derivatives as inhibitors of acetylcholinesterase.
Four different regioisomers of cationic bis-N,N-dimethylfulleropyrrolidinium salts have been prepared and evaluated as inhibitors of the enzymatic activity of acetylcholinesterase. These fullerene-based derivatives were found to be noncompetitive inhibitors of acetylthiocholine hydrolysis. Molecular modelling was used to describe the possible interactions between the fullerene cage and the amino acids surrounding the cavity of the enzyme. The cationic C(60) derivatives used in this study represent a new class of molecules potentially able to modulate the enzymatic activity of acetylcholinesterase.
Pastorin
Giorgia
G
Institute of Molecular and Cellular Biology, UPR 9021 CNRS, Strasbourg, France.
Marchesan
Silvia
S
Hoebeke
Johan
J
Da Ros
Tatiana
T
Ehret-Sabatier
Laurence
L
Briand
Jean-Paul
JP
Prato
Maurizio
M
Bianco
Alberto
A
D000110:Acetylcholinesterase / Q000187:drug effects*; D001665:Binding Sites; D002412:Cations; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D037741:Fullerenes / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular
D002412:Cations; D002800:Cholinesterase Inhibitors; D037741:Fullerenes; D000110:Acetylcholinesterase