卟啉介导抗癌药物的合成及其活性研究

目的设计合成新型替加氟卟啉化合物及其金属络合物，并评价其抗肿瘤活性。方法根据卟啉对肿瘤组织的选择性滞留作用，设计了3个卟啉替加氟化合物及3个金属络合物，并以吡咯和取代苯甲醛为原料经4步反应以满意的收率得到目标化合物。采用MTT法，以替加氟为阳性对照药，评价目标化合物对人结肠癌Lovo细胞株和人肝癌SMCC-7721细胞株的抗肿瘤活性；同时通过裸鼠体内抗肿瘤实验进一步评价金属络合物4b的体内抗肿瘤活性。结果合成了6个未见文献报道的新化合物，其结构经IR、UV-vis、1^H-NMR、MS及元素分析确证；体外活性实验表明，3个卟啉替加氟化合物表现出与替加氟相似的抗肿瘤活性，而3个金属络合物的抗肿瘤活性却是替加氟的两倍；金属络合物4b的体内肿瘤抑制率达70．4％。结论通过金属卟啉结构单元的引入可明显提高替加氟的抗肿瘤活性。

Synthesis of porphyrin induced anticancer drugs and their antitumor activities

Aim To design and synthesize novel ftorafur-porphyrin compounds and their metal derivatives, and to estimate their antitumor activities. Methods In view of the selective accumulation of porphyrin derivatives in tumor tissue, three ftorafur-porphyrin compounds and three metal compounds were designed, and the target compounds were synthesized with satisfied yield via a four-step procedure starting from pyrrol and substituted benzaldehydes. The antitumor activities of these new compounds to human colonic cancer Lovo cells and human liver cancer SMCC-7721 cells in vitro were evaluated by MTT assay, and the antitumor activities in vivo of metal compound 4b was tested further. Results Six novel ftorafur-porphyrin compounds were synthesized, and their structures were characterized by IR, UV-vis, ¹H-NMR, MS spectra and elementary analysis. The MTT results revealed that the antitumor activities of compounds 3a-3c were similar to that of ftorafur, however, the antitumor activity of metal compounds 4a-4c were about two times as large as that of ftorafur.And the inhibitory rate of compound 4b to Lovo cells in vivo was up to 70.4 %. Conclusion The antitumor activity of ftorafur could be improved obviously by binding a metal porphyrin block.