Benzofuran-based hybrid compounds for the inhibition of cholinesterase activity, beta amyloid aggregation, and abeta neurotoxicity.
The complex etiology of Alzheimer's disease (AD) prompts scientists to develop multitarget strategies to combat causes and symptoms. We therefore designed, synthesized, and tested new hybrid molecules linking a benzofuran ring to a N-methyl- N-benzylamine through a heptyloxy chain, affording a series of potential multifunctional drugs for AD. The cholinesterase inhibitory activity was extended to the inhibition of Abeta fibril formation for 1, 3, and 5. Compound 3 showed an additional neuroprotective effect.
Rizzo
Stefano
S
Department of Pharmaceutical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
Rivière
Céline
C
Piazzi
Lorna
L
Bisi
Alessandra
A
Gobbi
Silvia
S
Bartolini
Manuela
M
Andrisano
Vincenza
V
Morroni
Fabiana
F
Tarozzi
Andrea
A
Monti
Jean-Pierre
JP
Rampa
Angela
A
D000110:Acetylcholinesterase / Q000737:chemistry; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002091:Butyrylcholinesterase / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000682:Amyloid; D016229:Amyloid beta-Peptides; D001572:Benzofurans; D002800:Cholinesterase Inhibitors; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase