Home › Publications

Tacrine-based dual binding site acetylcholinesterase inhibitors as potential disease-modifying anti-Alzheimer drug candidates

Posted June 8th, 2010 by pschmidtke
TitleTacrine-based dual binding site acetylcholinesterase inhibitors as potential disease-modifying anti-Alzheimer drug candidates
Publication TypeJournal Article
Year of Publication2010
AuthorsCamps, P, Formosa X, Galdeano C, Gomez T, Munoz-Torrero D, Ramirez L, Viayna E, Gomez E, Isambert N, Lavilla R, Badia A, Clos MV, Bartolini M, Mancini F, Andrisano V, Bidon-Chanal A, Huertas O, Dafni T, Luque FJ
JournalChemico-biological interactions
Date Published2010/02/16/
AbstractTwo novel families of dual binding site acetylcholinesterase (AChE) inhibitors have been developed, consisting of a tacrine or 6-chlorotacrine unit as the active site interacting moiety, either the 5,6-dimethoxy-2-[(4-piperidinyl)methyl]-1-indanone fragment of donepezil (or the indane derivative thereof) or a 5-phenylpyrano[3,2-c]quinoline system, reminiscent to the tryciclic core of propidium, as the peripheral site interacting unit, and a linker of suitable length as to allow the simultaneous binding at both sites. These hybrid compounds are all potent and selective inhibitors of human AChE, and more interestingly, are able to interfere in vitro both formation and aggregation of the beta-amyloid peptide, the latter effects endowing these compounds with the potential to modify Alzheimer's disease progression.