卟啉硝基咪唑类衍生物的合成及放射增敏作用

Synthesis of porphyrin-nitroimidazole derivatives and their radiosensitization

目的设计合成卟啉硝基咪唑类化合物,评价其体外肿瘤放射增敏活性,寻找新的肿瘤放射增敏剂。方法以吡咯、苯甲醛、硝基咪唑为原料,经环合、溴代、取代、络合等反应合成卟啉硝基咪唑类化合物及其金属配合物。采用MTT法考查该系列衍生物对人宫颈癌Helo细胞株的放射增敏活性。结果合成了12个未见文献报道的新化合物,其结构经紫外光谱、ESI质谱、红外光谱和核磁共振氢谱确证。在4Gy照射剂量下,化合物15、16、18、19对人宫颈癌Helo细胞株显示出很好的放射增敏活性,对肿瘤细胞的抑制率达到95%左右。结论金属卟啉结构单元的引入,极大地提高了硝基咪唑类的放射增敏活性。

Aim To discover novel radiosensitizers of antitumor activities, a series of porphyrin-nitroimidazole derivatives were designed and synthesized and their radiosensitization were investigated. Methods Starting with pyrrole, benzaldehyde, nitroimidazole, followed by cyclization, bromination, substitution, and so on, a series of porphyrin-nitroimidazole derivatives and their metal chelating compounds were synthesized, and their radiosensitization in vitro to human Helo cells were evaluated by MTT method. Results Twelve novel compounds were synthesized, and their structures were characterized by UV-vis, ESI-MS, IR, and ^1H- NMR, Compounds 15, 16, 18 and 19 displayed good radiosensitivity to human cervix cancer cell Helo in vitro. The inhibition rates reached 95 % after they were exposed to X-ray at a dose of 4 Gy. Conclusion The radiosensitivity of nitroimidazole compounds can be improved by linking a metal porphyrin block.