As a continuation of our research in the quinoxaline 1,4-di-N-oxide new series of 2-arylcarbonyl-3-trifluoromethylquinoxaline, 1,4-di-N-oxide derivatives have been synthesized and evaluated in a full panel of 60 human tumor cell lines. Selective reductions were carried out on two compounds which allowed us to determine the compound structures by comparison of the 1H NMR spectra. In general, all the di-N-oxidized compounds showed good cytotoxic parameters. The best activity was observed in derivatives with electron-withdrawing groups in position 6 or 7 on the quinoxaline ring and in the unsubstituted analogues, whereas loss of one or two oxygens reduced the cytotoxicity. The best five compounds were selected for evaluation for the in vivo hollow fiber assays. In vitro studies reveal that compound 5h efficiently generates reactive oxygen species via redox cycling in the presence of the NADPH/cytochrome P450 enzyme system, providing a plausible molecular mechanism for the observed aerobic cytotoxicity of these quinoxaline N-oxides.

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.We report the synthesis, anti-inflammatory and antioxidant activities of novel quinoxaline and quinoxaline 1,4-di-N-oxide derivatives. Microwave assisted methods have been used in order to optimize reaction times and to improve the yields. The tested compounds presented important scavenging activities and promising in vitro inhibition of soybean lipoxygenase. Two of the best lipoxygenase inhibitors (compounds 7b and 8f) were evaluated as in vivo antiinflammatory agents using the carrageenin-induced edema model. One of them (compound 7b) showed important in vivo anti-inflammatory effect (41%) similar to that of indomethacin (47%) used as the reference drug.

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