Synthesis and evaluation of paramagnetic caffeic acid phenethyl ester (CAPE) analogs

The structure-activity relationships of newly prepared caffeates, containing nitroxide moieties as potential antioxidants have been investigated and compared to those of known natural (caffeic acid phenethyl ester, CAPE) and unnatural (N-acetylcysteine, paramagnetic alcohols) antioxidants. The in vitro antioxidant activity was tested by 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging, while assays of cell protection against reactive oxygen species were carried out in the presence of 2 ',7 '-dichlorofluorescein diacetate and H2O2. Paramagnetic esters without phenol motifs exhibited the lowest antioxidant activity, followed by paramagnetic alcohols with moderate activity. Among the compounds investigated, paramagnetic phenolic compounds were the best antioxidants. As the new paramagnetic CAPE analogs were less cytotoxic than CAPE at 10 mu M in NIH3T3 fibroblast cells but had similar antioxidant activity, they can be considered promising antioxidants. [GRAPHICS] .