Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/106286
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 UID/QUI/00100/2019 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. | URI: | https://hdl.handle.net/10316/106286 | ISSN: | 1475-6366 1475-6374 |
DOI: | 10.1080/14756366.2019.1689237 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais FMUC Medicina - Artigos em Revistas Internacionais |
Files in This Item:
WEB OF SCIENCETM
Citations
35
checked on May 2, 2023
Page view(s)
73
checked on Aug 28, 2024
Download(s)
39
checked on Aug 28, 2024
Google ScholarTM
Check
Altmetric
Altmetric
This item is licensed under a Creative Commons License