3-Hydroxy-4-pyridinone derivatives as metal ion and amyloid binding agents

Maria A. Telpoukhovskaia, Cristina Rodríguez-Rodríguez, Jacqueline F. Cawthray, Lauren E. Scott, Brent D.G. Page, Jorge Alí-Torres, Mariona Sodupe, Gwendolyn A. Bailey, Brian O. Patrick, Chris Orvig

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Metal ions have been implicated in several neurodegenerative diseases, including Alzheimer's disease, as their dyshomeostasis may lead to production of reactive oxygen species as well as increased toxicity of amyloid protein aggregates. In this work, we present design and synthesis of three novel multifunctional hydroxypyridinone ligands, HL11, HL12, and HL13, bearing benzothiazole and benzoxazole functionalities. We study the ability of these compounds to bind metal ions Cu(ii), Zn(ii), and Fe(iii), as well as their antioxidant activity and cytotoxicity. Additionally, we determine the pro-ligands' (compounds prior to chelation) propensity to target amyloid protein. Through these studies we determine the effect of combining amyloid- and metal-binding functionalities within the HPO scaffold on different aspects of AD pathology.

Original languageEnglish (US)
Pages (from-to)249-262
Number of pages14
JournalMetallomics
Volume6
Issue number2
DOIs
StatePublished - Feb 2014
Externally publishedYes

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