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Title: Novel tacrine-benzofuran hybrids as potential multi-target drug candidates for the treatment of Alzheimer's Disease
Authors: Fancellu, Gaia
Chand, Karam
Tomás, Daniel
Orlandini, Elisabetta
Piemontese, Luca
Silva, Diana F. 
Cardoso, Sandra M. 
Chaves, Sílvia
Santos, M. Amélia
Keywords: Alzheimer’s disease; multitarget drugs; tacrinebenzofuran hybrids; AChE inhibitors; metal chelators
Issue Date: Dec-2020
Publisher: Taylor and Francis Ltd
Project: UID/QUI/ 00100/2013 
postdoctoral fellowship (KC) 
Erasmus+ programme (GF) 
Portuguese NMR (IST-UL Center) 
Mass Spectrometry Networks (Grant LISBOA-01–0145- FEDER-022125) 
Serial title, monograph or event: Journal of Enzyme Inhibition and Medicinal Chemistry
Volume: 35
Issue: 1
Abstract: Pursuing the widespread interest on multi-target drugs to combat Alzheimer´s disease (AD), a new series of hybrids was designed and developed based on the repositioning of the well-known acetylcholinesterase (AChE) inhibitor, tacrine (TAC), by its coupling to benzofuran (BF) derivatives. The BF framework aims to endow the conjugate molecules with ability for inhibition of AChE (bimodal way) and of amyloid-beta peptide aggregation, besides providing metal (Fe, Cu) chelating ability and concomitant extra anti-oxidant activity, for the hybrids with hydroxyl substitution. The new TAC-BF conjugates showed very good activity for AChE inhibition (sub-micromolar range) and good capacity for the inhibition of self- and Cu-mediated Aβ aggregation, with dependence on the linker size and substituent groups of each main moiety. Neuroprotective effects were also found for the compounds through viability assays of neuroblastoma cells, after Aβ1-42 induced toxicity. Structure-activity relationship analysis provides insights on the best structural parameters, to take in consideration for future studies in view of potential applications in AD therapy.
ISSN: 1475-6366
DOI: 10.1080/14756366.2019.1689237
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais

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