Spin trapping and cytoprotective properties of fluorinated amphiphilic carrier conjugates of cyclic versus linear nitrones.
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 (H(2)O(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 H(2)O(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.
Durand
Grégory
G
Laboratoire de Chimie BioOrganique et des Systèmes Moléculaires Vectoriels, Faculté des Sciences, Université d'Avignon et des Pays de Vaucluse, 33 Rue Louis Pasteur, 84000 Avignon, France. gregory.durand@univ-avignon.fr
Prosak
Robert A
RA
Han
Yongbin
Y
Ortial
Stéphanie
S
Rockenbauer
Antal
A
Pucci
Bernard
B
Villamena
Frederick A
FA
D000447:Aldehydes / Q000633:toxicity; D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity; D002417:Cattle; D003432:Cross-Linking Reagents / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D042783:Endothelial Cells / Q000187:drug effects; D005461:Fluorine / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000633:toxicity; D008981:Molsidomine / Q000031:analogs & derivatives / Q000633:toxicity; D009589:Nitrogen Oxides / Q000737:chemistry* / Q000633:toxicity; D019097:Spin Trapping
D000447:Aldehydes; D000959:Antihypertensive Agents; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D009589:Nitrogen Oxides; C015388:nitrones; D005461:Fluorine; C002385:linsidomine; D006861:Hydrogen Peroxide; D008981:Molsidomine; C027576:4-hydroxy-2-nonenal
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