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-tetramethylpi peridine-1-oxyl) was synthesized and its antioxidant and antitumor propel-t ies were investigated and compared with these of another nitroxide derivati ves 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 con stant of the reactions of Metexyl with enzymatically generated O-2(.-) or r adiolytically produced (OH)-O-.. For comparison, the reactions of non radic al derivative (4-acetamide-2,2, 6, 6-tetramethylpiperidinium acetate) or ni troxide Tempace (4-acetamide-2,2 6, 6-tetramethylpiperidine-1-oxyl) with th e above mentioned reactive oxygen radicals were also studied. The comparati ve ability of Metexyl to act as an inducer of apoptosis in vivo was also in vestigated in pharmacological test. The ring substituent (-OCH3) at positio n 4 of the Metexyl molecule had significant influence on its properties as antioxidant and apoptosis inducer: The results ill 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.