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https://hdl.handle.net/10316/103766
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) UID/QUI/00100/2019 POCI-01-0145-FEDER-030712 |
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. | URI: | https://hdl.handle.net/10316/103766 | 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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biomolecules-11-00111-v2.pdf | 4.74 MB | Adobe PDF | View/Open |
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