Tempicol-2 (4-hydroxy-4-(2-picolyl)-2,2,6,6-tetramethylpiperidine-1-oxyl), a stable free radical, is a novel member of nitroxide class of antioxidants and anticancer agents.
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.
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Institute of Applied Radiation Chemistry, Technical University of Lodź, Poland. media@mitr.p.lodz.pl
Skolimowski
J
J
Kochman
A
A
Gwozdzinski
K
K
Głebska
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D003855:Deoxyribose / Q000737:chemistry; D005260:Female; D005609:Free Radicals; D008297:Male; D009580:Nitroblue Tetrazolium / Q000737:chemistry; D010084:Oxidation-Reduction; D011725:Pyridines / Q000494:pharmacology*; D011837:Radiation-Protective Agents; D051381:Rats; D017382:Reactive Oxygen Species; D012513:Sarcoma, Experimental; D013481:Superoxides / Q000737:chemistry; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D000975:Antioxidants; D003497:Cyclic N-Oxides; D005609:Free Radicals; D011725:Pyridines; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; C111839:tempicol 2; D013481:Superoxides; D009580:Nitroblue Tetrazolium; D003855:Deoxyribose; D001205:Ascorbic Acid