ELECTRON-AFFINIC SENSITIZATION .7. CORRELATION BETWEEN STRUCTURES ONE-ELECTRON REDUCTION POTENTIALS, AND EFFICIENCIES OF NITROIMIDAZOLES AS HYPOXIC CELL RADIOSENSITIZERS
ELECTRON-AFFINIC SENSITIZATION .7. CORRELATION BETWEEN STRUCTURES ONE-ELECTRON REDUCTION POTENTIALS, AND EFFICIENCIES OF NITROIMIDAZOLES AS HYPOXIC CELL RADIOSENSITIZERS
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DOI：
10.2307/3574491
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发表时间：
1976-01-01
影响因子：
3.4
通讯作者：
WATTS, ME
中科院分区：
文献类型：
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作者：
ADAMS, GE;FLOCKHART, IR;WATTS, ME
在体外X射线照射的低氧中国人膀胱癌细胞系V79- 379 A中，测定了Ro-070582 [1-（2-羟基-3-甲氧丙基）-2-硝基咪唑]及其尿代谢产物Ro-05-9963 [1-（2-甲氧基-3-甲氧丙基）-2-硝基咪唑]和2种5-硝基咪唑（包括甲硝唑）的放射增敏作用。所有化合物均为活性低氧细胞增敏剂，增敏率随药物浓度增加而增加。2-硝基咪唑类均比5-硝基咪唑类更有效。总体而言，效率（定义为给出特定增强比所需的浓度）的变化系数约为200。用脉冲辐解法测定了敏化剂的电子亲合势作为单电子还原电位，这些与化合物的敏化效率有很好的相关性。相关性延伸到硝基咪唑系列以外，如对硝基苯乙酮、硝呋辛（一种硝基呋喃）和氧本身的数据所示。硝基咪唑的辛醇/水分配系数变化的70倍，但这个参数对敏化效率的影响与电子亲和势的影响相比是小的。
Radiosensitization efficiencies for 7 different 2-nitroimidazoles including Ro-070582 [1-(2-hydroxy-3-methoxypropyl)-2-nitroimidazole] and its urinary metabolite, Ro-05-9963, [1-(2-methoxy-3-methoxypropyl)-2-nitroimidazole] and 2 5-nitroimidazoles including metronidazole, were determined in hypoxic Chinese Hamster cells, line V79-379A, X-irradiated in vitro. All the compounds were active hypoxic cell sensitizers with the enhancement ratios increasing with drug concentration. The 2-nitroimidazoles were all more efficient than the 5-nitroimidazoles. Overall, the efficiencies, defined as the concentration required to give a particular enhancement ratio, varied by a factor of about 200. Electron-affinities of the sensitizers were determined by pulse radiolysis as the one-electron reduction potentials and these correlate well with the sensitization efficiencies of the compounds. The correlation extends beyond the nitroimidazole series as is shown by data for p-nitroacetophenone, nifuroxime (a nitrofuran) and oxygen itself. The nitroimidazoles varied by a factor of 70 in their octanol/water partition coefficients, but the effect of this parameter on sensitizing efficiency is small compared with the influence of electron affinity.