As a part of our studies on the chemical, biochemical and pharmacological characteristics of the newly synthesized
antioxidants,
nitroxide derivatives, we designed a novel
nitroxide, named
Tempicol-2. Its capacity to act as
antioxidant of potential pharmacological application was tested in three model systems:
xanthine/
xanthine oxidase,
iron- and ascorbate Fenton reaction(s) and gamma-radiolysis. The
antioxidant properties of
Tempicol-2 as a function of concentration were compared with those previously characterized
nitroxide derivatives
Tempace and Rutoxyl which we had synthesized. The possibility of one-electron reduction of the novel substance by
ascorbic acid was also examined and compared. The ability of
Tempicol-2 to act as
anticancer agent in vivo was also investigated in pharmacologic tests. The administration of
Tempicol-2 to rats bearing 3 day-old
Yoshida Sarcoma (promotion phase) led to both growth inhibition and the induction of apoptotic cells(s) death, comparable to the effects of
Tempace and Rutoxyl under the same experimental conditions. Our results confirmed the suggested involvement of
free radicals in the pathogenesis of model.
Yoshida Sarcoma, thus indicating that anticancer activity of the investigated nitroxides may indirectly involve an
antioxidant mechanism. The results reported here are encouraging as we find a limited correlation between the molecular redox properties, structure of nitroxides and their antitumor action.
Tempicol-2, similarly to
Tempace and Rutoxyl, is a promising
antioxidant which can induce apoptosis, thus providing the basis for further investigations of the concentration and phase-dependent effects and the exact mechanisms of
nitroxide(s) apoptotic action using cell line(s) model.