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

Pelayo Camps, Xavier Formosa, Carles Galdeano, Tània Gómez, Diego Muñoz-Torrero, Lorena Ramírez, Elisabet Viayna, Elena Gómez, Nicolás Isambert, Rodolfo Lavilla, Albert Badia, M. Victòria Clos, Manuela Bartolini, Francesca Mancini, Vincenza Andrisano, Axel Bidon-Chanal, Óscar Huertas, Thomai Dafni, F. Javier Luque

Research output: Contribution to journalArticleResearchpeer-review

63 Citations (Scopus)

Abstract

Two 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 β-amyloid peptide, the latter effects endowing these compounds with the potential to modify Alzheimer's disease progression. © 2010 Elsevier Ireland Ltd.
Original languageEnglish
Pages (from-to)411-415
JournalChemico-Biological Interactions
Volume187
Issue number1-3
DOIs
Publication statusPublished - 1 Jan 2010

Keywords

  • Acetylcholinesterase
  • Dual binding site inhibitors
  • β-Amyloid
  • β-Secretase

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