piperidines and tempace

The piperidine nitroxides Tempamine and Tempace have been studied for their effect on doxorubicin (DOX) and hydrogen peroxide (H(2)O(2)) cytotoxicity in immortalized B14 cells, a model for neoplastic phenotype. The significance for nitroxide performance of the substituent in position 4 of the piperidine ring was evaluated. The cells were exposed to DOX/H(2)O(2) alone or in combination with the nitroxides Tempamine or Tempace. Two other piperidine nitroxides, Tempo and Tempol, were used for comparison. All the nitroxides except Tempamine modestly reduced DOX cytotoxicity. Tempamine evoked a biphasic response: at concentrations lower than 200 micromol/L the nitroxide decreased DOX cytotoxicity, while at concentrations higher than 200 micromol/L, it enhanced DOX cytotoxicity. In contrast to Tempo and Tempol, Tempamine and Tempace ameliorated hydrogen peroxide cytotoxicity, but none of the nitroxides influenced TBARS stimulated by hydrogen peroxide. The cytoprotective effect of Tempace, Tempo and Tempol in DOX-treated cells correlated with the inhibition of DOX-induced lipid peroxidation. The bioreduction rates of the investigated nitroxides differed significantly and were variously affected by DOX depending on the nitroxide substituent. In combination with DOX, Tempo and Tempol were reduced significantly more slowly, while no influence of DOX on Tempamine and Tempace bioreduction was observed. Our results suggest that the structure of the 4-position substituent is an important factor for biological activity of piperidine nitroxides. Among the investigated nitroxides, Tempace displayed the best protective properties in vitro but Tempamine was the only nitroxide that potentiated cytotoxicity of DOX and did not influence DOX-induced lipid peroxidation. However, this nitroxide showed different performance depending on its concentration and conditions of oxidative stress.

Topics: Animals; Cell Death; Cell Line; Cell Membrane; Cell Survival; Cricetinae; Cricetulus; Cyclic N-Oxides; Cytoprotection; Doxorubicin; Electron Spin Resonance Spectroscopy; Hydrogen Peroxide; Lipid Peroxidation; Oxidation-Reduction; Oxidative Stress; Piperidines; Spin Labels

A novel complex, Rutoxyl [rutin/4-acetamide-1-hydroxy-2,2,6,6-tetramethylpiperidinium] was synthesized and its structure and anticancer activity were investigated. The results reported here are consistent with our idea, that the formation of such a complex of two biologically active molecules: polyphenolic flavonoid antioxidant (Rutin) and nitroxylamine of nitroxide antioxidant (Tempace), stabilized by hydrogen bond(s) can result in a supra-additive properties.

Topics: Animals; Antineoplastic Agents; Antioxidants; Cyclic N-Oxides; Drug Design; Drug Screening Assays, Antitumor; Male; Models, Molecular; Molecular Structure; Piperidines; Rats; Rats, Wistar; Rutin; Sarcoma, Experimental; Structure-Activity Relationship

Two novel 2,2,6,6-tetramethylpiperidine derivatives (Tempace and Troxyl) were synthesized and their capacity to act as scavengers of superoxide, inhibitors of iron and ascorbate-driven Fenton reaction and radioprotectors was tested. The possibility for one-electron oxidation of novel compounds by heme-ferryl species was also examined. The results clearly indicate that Tempace and Troxyl are acting as promising antioxidants and radioprotectors thus providing a base for further investigations and pharmacological applications.

Topics: Antioxidants; Cobalt Radioisotopes; Cyclic N-Oxides; Deoxyribose; Dose-Response Relationship, Drug; Free Radical Scavengers; Hydrogen Peroxide; Hydroxyl Radical; Iron; Oxidation-Reduction; Piperidines; Radiation-Protective Agents; Spin Labels; Superoxide Dismutase; Superoxides; Thiobarbituric Acid Reactive Substances; Xanthine; Xanthine Oxidase; Xanthines