TY - JOUR
T1 - 3-Hydroxy-4-pyridinone derivatives as metal ion and amyloid binding agents
AU - Telpoukhovskaia, Maria A.
AU - Rodríguez-Rodríguez, Cristina
AU - Cawthray, Jacqueline F.
AU - Scott, Lauren E.
AU - Page, Brent D.G.
AU - Alí-Torres, Jorge
AU - Sodupe, Mariona
AU - Bailey, Gwendolyn A.
AU - Patrick, Brian O.
AU - Orvig, Chris
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
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U2 - 10.1039/c3mt00135k
DO - 10.1039/c3mt00135k
M3 - Article
C2 - 23999879
AN - SCOPUS:84893257879
SN - 1756-5901
VL - 6
SP - 249
EP - 262
JO - Metallomics
JF - Metallomics
IS - 2
ER -