Development of an iron-selective antioxidant probe with protective effects on neuronal function

dc.creatorGarc?a-Beltr?n, Olimpo
dc.creatorMena, Natalia P.
dc.creatorAguirre, Pabla
dc.creatorBarriga-Gonz?lez, Germ?n
dc.creatorGald?mez, Antonio
dc.creatorNagles, Edgar
dc.creatorAdasme, Tatiana
dc.creatorHidalgo, Cecilia
dc.creatorN??ez, Marco T.
dc.date2019-03-01T16:31:41Z
dc.date2019-03-01T16:31:41Z
dc.date2017-12-15
dc.date.accessioned2023-08-31T19:22:34Z
dc.date.available2023-08-31T19:22:34Z
dc.identifierGarc?a-Beltr?n O, Mena NP, Aguirre P, Barriga-Gonz?lez G, Gald?mez A, Nagles E, et al. (2017) Development of an iron-selective antioxidant probe with protective effects on neuronal function. PLoS ONE 12(12)
dc.identifier1932-6203
dc.identifierhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0189043
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8557579
dc.descriptionIron accumulation, oxidative stress and calcium signaling dysregulation are common pathognomonic signs of several neurodegenerative diseases, including Parkinson?s and Alzheimer?s diseases, Friedreich ataxia and Huntington?s disease. Given their therapeutic potential, the identification of multifunctional compounds that suppress these damaging features is highly desirable. Here, we report the synthesis and characterization of N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-2-(7-hydroxy-2-oxo-2H-chromen-4-yl)acetamide, named CT51, which exhibited potent free radical neutralizing activity both in vitro and in cells. CT51 bound Fe2+ with high selectivity and Fe3+ with somewhat lower affinity. Cyclic voltammetric analysis revealed irreversible binding of Fe3+ to CT51, an important finding since stopping Fe2+/Fe3+ cycling in cells should prevent hydroxyl radical production resulting from the Fenton-Haber-Weiss cycle. When added to human neuroblastoma cells, CT51 freely permeated the cell membrane and distributed to both mitochondria and cytoplasm. Intracellularly, CT51 bound iron reversibly and protected against lipid peroxidation. Treatment of primary hippocampal neurons with CT51 reduced the sustained calcium release induced by an agonist of ryanodine receptor-calcium channels. These protective properties of CT51 on cellular function highlight its possible therapeutic use in diseases with significant oxidative, iron and calcium dysregulation.
dc.languageen
dc.publisherPLoS ONE
dc.subjectNeuronal function
dc.subjectAntioxidants
dc.titleDevelopment of an iron-selective antioxidant probe with protective effects on neuronal function
dc.typeArticle


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