Spin trapping and cytoprotective properties of fluorinated amphiphilic carrier conjugates of cyclic versus linear nitrones

Grégory Durand, Robert A. Prosak, Yongbin Han, Stéphanie Ortial, Antal Rockenbauer, Bernard Pucci, Frederick A. Villamena

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Abstract

Nitrones have been employed as spin trapping reagent as well as pharmacological agent against neurodegenerative diseases and ischemia-reperfusion induced injury. The structure-activity relationship was explored for the two types of nitrones, i.e., cyclic (DMPO) and linear (PBN), which are conjugated to a fluorinated amphiphilic carrier (FAC) for their cytoprotective properties against hydrogen peroxide (H2O 2), 3-morpholinosynonimine hydrochloride (SIN-1), and 4-hydroxynonenal (HNE) induced cell death on bovine aortic endothelial cells. The compound FAMPO was synthesized and characterized, and its physical-chemical and spin trapping properties were explored. Cytotoxicity and cytoprotective properties of various nitrones either conjugated and nonconjugated to FAC (i.e., AMPO, FAMPO, PBN, and FAPBN) were assessed using a 3-[4,5-dimethylthiazol-2-yl] -2,5-diphenyltetrazolium (MTT) reduction assay. Results show that of all the nitrones tested, FAPBN is the most protective against H2O 2, but FAMPO and to a lesser extent its unconjugated form, AMPO, are more protective against SIN-1 induced cytotoxicity. However, none of the nitrones used protect the cells from HNE-induced cell death. The difference in the cytoprotective properties observed between the cyclic and linear nitrones may arise from the differences in their intrinsic antioxidant properties and localization in the cell.

Original languageEnglish
Pages (from-to)1570-1581
Number of pages12
JournalChemical Research in Toxicology
Volume22
Issue number9
DOIs
Publication statusPublished - Sep 21 2009

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ASJC Scopus subject areas

  • Toxicology

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