稳定氮氧自由基TMPO和TMPRO的合成与应用

本文评述了近年来4-氧-2,2,6,6-四甲基哌啶-1-氧自由基(TMPO)和2,2,5,5-四甲基吡咯啉-1-氧自由基(TMPRO)及其衍生物在合成和应用方面的进展,着重讨论了这些氮氧自由基的合成方法和作为自旋标记试剂的应用。     

N-(2,2,5,5-四甲基-3-吡咯啉-1-氧自由基)-N-(酰胺基)脲化合物的合成及抗癌活性

本文合成19个新的N-(2,2,5,5-四甲基-3-吡咯啉-1-氧自由基)-N-(酰胺基)脲化合物.研究了此类化合物的ESR,MS及IR波谱性质.初步观察了此类化台物对白血病L7712癌细胞以及腹水型肝癌细胞的抑制作用.发现有的化合物抑制效果显著.     

DNA SYNTHESIS INHIBITION OF NITROXIDE RADICALS ON LEUKEMIA CELLS

4-isothiocyanate-2,2,6,6-tetramethyl-piperidine-l-oxyl has the strongest effects on the DNA synthesis and viability of isolated leukemia 7712 cells. This compound is a very potent inhibitor of DNA synthesis with 50% inhibition of cell DNA synthesis occurring at 2.2 μg/ml, while the LD50 for white mice is 277 mg/kg. During the concentration of 50 μg/ml, the inhibition of DNA synthesis is 99.7%, which is unable to damage the DNA replicate templet. The inhibition of this compound, a combination of nitroxide and isothiocyanate, appears to be stronger than that of the sum of the two separate actions. Much more moderate effects are seen for all the other nitroxide radicals. After reducing nitroxide to hydroxyla-mine, there is no inhibition for DNA synthesis. The free radical mechanism of carcinogene-sis and antitumor action has been discussed.     

氮氧自由基对白血病细胞DNA合成的抑制

4-异硫氰酸盐-2,2,6,6-四甲基哌啶-1-氧自由基对白血病细胞7712的生长及DNA合成都有强烈抑制作用,对DNA合成的半抑制浓度为2.2μg/ml,在浓度为50μg/ml时抑制率高达99.7％,对小白鼠腹腔注射的半致死剂量为277mg/kg,不损伤DNA复制模板。它对DNA合成的抑制作用强于异硫氰酸盐及氮氧自由基单独作用之和。其它氮氧自由基类化合物也有较弱的抑制作用。但氮氧自由基的还原物羟胺却没有抑制作用。对致癌和抗癌的自由基机理进行了讨论。