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目的合成硝基咪唑类血卟啉衍生物,测定其体外抗肿瘤活性。方法以血红素为原料,首先制备血卟啉二甲醚,然后用4-二甲氨基吡啶为催化剂、二环己基碳二亚胺为脱水剂,在室温下,催化血卟啉二甲醚与甲硝唑缩合成酯;下腹部穿刺抽取接种了腹水瘤细胞H22的小鼠腹水瘤细胞,以台盼兰排染法测试体外的抑瘤活性。结果合成得到血卟啉二甲醚-双甲硝唑(HDMEM2)、血卟啉二甲醚-单甲硝唑异脲(HDMEM1)一对异构体,收率分别达50%、21%,其结构通过紫外、红外、核磁及质谱得到确证;两种化合物在57.5～240.0μg.mL-1对腹水瘤细胞H22的杀伤率均超过50%,IC50分别为0.103、0.101μmol.mL-1。结论 HDMEN2与HDMEN1仍保持着原料血卟啉的光谱性质,且有良好的体外抑瘤活性。
Objective To synthesize nitroimidazole hematoporphyrin derivative and determine its anti-tumor activity in vitro. Methods Heme as raw material, the first preparation of hematoporphyrin dimethyl ether, and then with 4-dimethylaminopyridine as a catalyst, dicyclohexyl carbodiimide as dehydrating agent at room temperature, catalytic hematoporphyrin dimethyl ether and Metronidazole condensation into esters; ascites tumor of ascites tumor cells inoculated ascites tumor cells in mice ascites tumor cells to trypan blue dye test in vitro antitumor activity. Results A pair of isomers of hematoporphyrin-metronidazole (HDMEM2) and hematoporphyrin-metronidazole iso-urea (HDMEM1) were synthesized and the yields were 50%, 21% Their structures were confirmed by UV, IR, NMR and MS spectra. The killing rates of the two compounds were all over 50% at 57.5 ~ 240.0μg.mL-1 for H22 ascites tumor cells with IC50 of 0.103 and 0.101μmol.mL-1, respectively. Conclusion HDMEN2 and HDMEN1 still maintain the spectroscopic properties of hematoporphyrin and have good antitumor activity in vitro.