STRUCTURE-ACTIVITY-RELATIONSHIPS IN THE DEVELOPMENT OF HYPOXIC CELL RADIOSENSITIZERS .1. SENSITIZATION EFFICIENCY
STRUCTURE-ACTIVITY-RELATIONSHIPS IN THE DEVELOPMENT OF HYPOXIC CELL RADIOSENSITIZERS .1. SENSITIZATION EFFICIENCY
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DOI：
10.1080/09553007914550151
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发表时间：
1979-01-01
影响因子：
2.6
通讯作者：
SMITHEN, CE
中科院分区：
文献类型：
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作者：
ADAMS, GE;CLARKE, ED;SMITHEN, CE
测定了 35 种硝基芳香族和硝基杂环化合物在体外对缺氧中国仓鼠细胞放射增敏的效率。测量了实现增强比 1.6 所需的化合物浓度 C，并将氧化还原和分配特性分别量化为 pH 7 时的 1 电子还原电势 E 和辛醇：水分配系数 P。大多数研究的化合物是2-硝基咪唑，但也研究了一些4-和5-硝基咪唑、5-硝基呋喃和硝基苯以进行比较。结合之前报道的 9 种硝基咪唑的数据，使用多元线性回归分析将结果拟合为 -log C = b0 + b1E + b2 log P + b3 (log P)2 形式的结构-活性关系。统计测试表明，系数b2和b3与零没有显着差异，并且通过省略log P中的项而获得的更简单的方程解释了log C中85％的方差。早期报道证实硝基化合物的体外放射增敏效率很大程度上取决于还原电位。 P 在体外不重要的结论性证明对于解释体内实验结果很有价值，预计 P 对生物反应有更大的影响。
The efficiency of 35 nitroaromatic and nitroheterocyclic compounds in radiosensitizing hypoxic Chinese Hamster cells in vitro was determined. The concentration C of the compound required to achieve an enhancement ratio of 1.6 was measured, and the redox and partition properties were quantified as the 1-electron reduction potential at pH 7, E and the octanol:water partition coefficient, P, respectively. Most of the compounds studied were 2-nitroimidazoles, but some 4- and 5-nitroimidazoles, 5-nitrofurans and nitrobenzenes were investigated for comparison. Together with data for 9 nitroimidazoles previously reported, the results were fitted to a structure-activity relationship of the form -log C = b0 + b1E + b2 log P + b3 (log P)2 using multiple linear regression analysis. Statistical tests showed that the coefficients b2 and b3 were not significantly different from zero and the simpler equation, obtained by omitting the terms in log P, explained 85% of the variance in log C. Earlier reports that the radiosensitization efficiency of nitro compounds in vitro largely depends on the reduction potential were confirmed. The conclusive demonstration that P is unimportant in vitro is valuable in interpreting the results of experiments in vivo, where P is expected to have a much greater influence on biological response.