Metexyl (4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxyl) as an oxygen radicals scavenger and apoptosis inducer in vivo.

A stable nitroxide radical named Metexyl (4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxyl) was synthesized and its antioxidant and antitumor properties were investigated and compared with these of another nitroxide derivatives previously designed in our laboratories. Three experimental models were used: xanthine/xanthine oxidase system, pulse radiolysis and experimental rat cancer (Yoshida Sarcoma) in vivo. In this work we measured the rate constant of the reactions of Metexyl with enzymatically generated O2.- or radiolytically produced .OH. For comparison, the reactions of non radical derivative (4-acetamide-2,2,6,6-tetramethylpiperidinium acetate) or nitroxide Tempace (4-acetamide-2,2,6,6-tetramethylpiperidine-1-oxyl) with the above mentioned reactive oxygen radicals were also studied. The comparative ability of Metexyl to act as an inducer of apoptosis in vivo was also investigated in pharmacological test. The ring substituent (-OCH3) at position 4 of the Metexyl molecule had significant influence on its properties as antioxidant and apoptosis inducer. The results in this study suggest that Metexyl is a promising nitroxide antioxidant, which can induce apoptosis of tumor cells in vivo, thus providing a base for its further investigations in vitro and pharmacological applications.