Artigo Revisado por pares

Cholinesterase Inhibitors: Xanthostigmine Derivatives Blocking the Acetylcholinesterase-Induced β-Amyloid Aggregation

2005; American Chemical Society; Volume: 48; Issue: 13 Linguagem: Inglês

10.1021/jm049515h

ISSN

1520-4804

Autores

Federica Belluti, Angela Rampa, Lorna Piazzi, Alessandra Bisi, Silvia Gobbi, Manuela Bartolini, Vincenza Andrisano, Andrea Cavalli, Maurizio Recanatini, Piero Valenti,

Tópico(s)

Alzheimer's disease research and treatments

Resumo

In continuing research that led us to identify a new class of carbamate derivatives acting as potent (Rampa et al. J. Med. Chem. 1998, 41, 3976) and long-lasting (Rampa et al. J. Med. Chem. 2001, 44, 3810) acetylcholinesterase (AChE) inhibitors, we obtained some analogues able to simultaneously block both the catalytic and the β-amyloid (Aβ) proaggregatory activities of AChE. The key feature of these derivatives is a 2-arylidenebenzocycloalkanone moiety that provides the ability to bind at the AChE peripheral site responsible for promoting the Aβ aggregation. The new carbamates were tested in vitro for the inhibition of both cholinesterases and also for the ability to prevent the AChE-induced Aβ aggregation. All of the compounds had AChE IC50 values in the nanomolar range and showed the ability to block the AChE-induced Aβ aggregation, thus supporting the feasibility of this new strategy in the search of compounds for the treatment of Alzheimer's disease.

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