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Title: Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer's Disease Agents
Authors: Poliseno, Viviana
Chaves, Sílvia
Brunetti, Leonardo
Loiodice, Fulvio
Carrieri, Antonio
Laghezza, Antonio
Tortorella, Paolo
Magalhães, João D. 
Cardoso, Sandra M. 
Santos, M. Amélia 
Piemontese, Luca
Keywords: Alzheimer’s disease; tenuazonic acid; donepezil; neurodegenerative; metal chelation; multifunctional drugs; acetylcholinesterase; antioxidant; amyloid
Issue Date: 15-Jan-2021
Publisher: MDPI AG
Project: Università degli Studi di Bari “Aldo Moro” and Regione Puglia (Fondo di Sviluppo e Coesione 2007–2013, APQ Ricerca Regione Puglia “Programma regionale a sostegno della specializzazione intelligente e della sostenibilità sociale ed ambientale— FutureInResearch”—Project ID: I2PCTF6) 
Serial title, monograph or event: Biomolecules
Volume: 11
Issue: 1
Abstract: Alzheimer's disease (AD) is generally recognized as a multifactorial neurodegenerative pathology with an increasing impact on society. Tenuazonic acid (TA) is a natural compound that was recently identified as a potential multitarget ligand with anti-cholinesterase, anti-amyloidogenic and antioxidant activities. Using its structure as a chemical scaffold, we synthesized and evaluated new derivatives (1-5), including tenuazonic-donepezil (TA-DNP) hybrids (4 and 5) due to the clinical importance of the anti-AD drug donepezil. These novel compounds all achieved activity in the micromolar range towards all selected targets and demonstrated to be potentially orally absorbed. Moreover, a selected compound (1) was further investigated as a chelating agent towards copper (II), zinc (II) and iron (III) and showed good chelating ability (pFe = 16.6, pCu = 11.6, pZn = 6.0 at pH 7.4). Therefore, the TA motif can be considered an interesting building block in the search for innovative multi-functional anti-neurodegenerative drugs, as exemplified by hybrid 5, a promising non-cytotoxic lead compound adequate for the early stages of AD, and capable of ameliorating the oxidative status of SH-SY5Y human neuroblastoma cells.
ISSN: 2218-273X
DOI: 10.3390/biom11010111
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais

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