血卟啉硝基咪唑类衍生物的合成及抗肿瘤活性初探  

Synthesis and antitumor activity of blood porphyrin-nitro imidazole derivatives

作　　者：崔瑜霞[1] 李秀玲[1] 何菱[1] 余蓉[1] 

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《华西药学杂志》2012年第5期517-520,共4页West China Journal of Pharmaceutical Sciences

摘　　要：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 blood porphyrin-nitro imidazole derivatives and investigate their antitumor activities in vitro.METHODS HDME was synthesized with heme first,then using DMAP as catalyst,DCC as dehydrating agent,HDME and Metronidazole,blood porphyrin-nitro imidazole derivatives were gene rated.Antitumor activities in vitro were tested with the method of Trypan blue staining.RESULTS HDMEM2 and HDMEM1 were synthesized,the yields of both compounds were 50% and 21%,respectively,and their structures were characterized by UV,IR,1HNMR and MS.The killing rate of the derivativeson tumor cell H22 exceeded 50% both;The IC50 of HDMEM2 and HDMEM1 were 0.103 and 0.101 μmol·mL-1.CONCLUSION The new compounds had the same spectroscopic properties and good antitumor activities in vitro.

关 键 词：血卟啉 血卟啉二甲醚 硝基咪唑 抗肿瘤 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]