Antioxidant properties of propargylamine derivatives: assessment of their ability to scavenge peroxynitrite.
A series of arylpropargylamines, variously substituted in the hydrogen in p-position and in the propargyl moiety, were studied as potential peroxynitrite scavengers. The scavenging activity of these compounds was evaluated through peroxynitrite (ONOO-)-mediated oxidation of dichlorofluorescin and linoleic acid by measuring the dichlorofluorescein formation and oxygen consumption, respectively. Among tested compounds, only 1-phenylpropargylamine (AP3) promoted concentration-dependent inhibition of ONOO(-)-induced dichlorofluorescin and linoleic acid oxidation with IC50 values of 637 and 63 microM, respectively. The AP3 spectral changes in UV-visible absorbance properties in the presence of peroxynitrite suggested the formation of a new compound. This was identified by gas-chromatograph-mass spectrometer analysis as phenylpropargyl alcohol. Structure-activity relationship analysis indicated that the scavenging activity of AP3 was due to the aminopropargyl moiety and availability of the nitrogen electron pair. This data suggested that AP3 could be considered a lead compound for the synthesis of new ONOO- scavenger derivatives.
Dragoni
Stefania
S
Dipartimento di Scienze Biomediche, Università di Siena, Via Aldo Moro 2, 53100 Siena, Italy.
Porcari
Valentina
V
Travagli
Massimo
M
Castagnolo
Daniele
D
Valoti
Massimo
M
D000975:Antioxidants / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D010293:Pargyline / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D011437:Propylamines / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*
D000975:Antioxidants; D016166:Free Radical Scavengers; D011437:Propylamines; D030421:Peroxynitrous Acid; C009054:propargylamine; D010293:Pargyline