The development of some nitroimidazoles as hypoxic cell sensitizers.
The development of some nitroimidazoles as hypoxic cell sensitizers.
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一些硝基咪唑作为缺氧细胞敏化剂的开发。
DOI：
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发表时间：
1980
期刊：
影响因子：
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通讯作者：
E. Fielden
中科院分区：
文献类型：
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作者：
G. Adams;P. O'Neill;I. Ahmed;I. Stratford;E. Fielden
目前，用于放射治疗的最有希望的低氧细胞增敏剂是2-硝基咪唑、米索咪唑，尽管神经毒性阻止其在最佳结果所需的剂量下使用。在寻找具有更好的治疗比率的药物时，我们研究了几类取代的2-，4-和5-硝基咪唑。一般来说，2-硝基衍生物是最有效的，符合电子亲和力的考虑。然而，值得注意的例外包括一些在5-位被各种磺酰胺或磺酸盐基团取代的4-硝基咪唑。这些化合物中的一些在浓度基础上与氧一样有效，并且显示出比从其电子亲合性预测的更大的活性。将描述使用这些化合物的细胞研究。此外，在2-硝基咪唑系列的N1侧链终止与吗啉，哌啶，和吡咯烷基团的链长的效果进行了研究。尽管这些化合物中的电子亲和力相当恒定，但结果表明，敏化效率和细胞毒性的系统性变化可以随着链长的变化而发生，这表明可能有可能提高治疗率。这些和其他研究将被用作在寻找更好的缺氧细胞敏化剂的方法的例子。
The most promising hypoxic cell sensitizer for use in radiotherapy is, at present, the 2-nitroimidazole, misonidazole, although neurotoxicity prevents its use at dosages necessary for optimum results. In the search for agents with better therapeutic ratios, we have investigated several classes of substituted 2-, 4-, and 5-nitroimidazoles. In general, 2-nitro derivatives are the most efficient in line with electron affinity considerations. However, notable exceptions include some 4-nitroimidazoles substituted in the 5-position by various sulphonamide or sulphonate groups. Some of these compounds are as efficient as oxygen on a concentration basis and display activity greater than predicted from their electron affinities. Cellular studies with these compounds will be described. Further, in the 2-nitroimidazole series the effect of the chain length of the N1 side chain terminated with a morpholine, piperidine, and pyrrolidine group has been studied. Notwithstanding the fairly constant electron affinities in these compounds, results show that systematic changes in sensitizing efficiency and cytotoxicity can occur with varying chain length, which indicates possible potential for increasing therapeutic ratio. These and other studies will be used as examples of the methods used in the search for better hypoxic cell sensitizers.