苯氧基磷酰氮芥取代的槐定碱衍生物的合成及其抗肿瘤活性研究

目的 设计合成苯氧基磷酰氮芥取代的槐定碱衍生物，并对其进行体外抗肿瘤活性研究。方法 以槐定碱为起始原料，经开环、酯化、磷酰化等反应合成目标化合物2a ～2e ，采用MTT法测定其对S180、H22、K562、MCF-7、SMMC-7721、LoVo肿瘤细胞的抑制活性。结果 设计并合成了5个目标化合物，其结构经¹H-NMR和ESI-MS确证。体外细胞测试结果显示所有化合物对S180和H22细胞株活性较强，且对正常细胞L929毒性小，部分化合物活性高于阳性对照药多柔比星。结论 目标化合物具有较强的抗肿瘤活性，化合物2b 为有潜力的候选化合物。

Synthesis of phenoxy-phosphoramidate mustard substituted sophoridinic derivatives and their antitumor activities

Objective To design and synthesize phenoxy-phosphoramidate mustard substituted sophoridinic derivatives, and to study their antitumor activities. Methods Sophoridine was used as the starting material to synthesize the target compounds 2a -2e via ring-opening, esterification and phosphorylation reaction. The inhibitory activity against S180, H22, K562, MCF-7, SMMC-7721, and LoVo tumor cells was determined by MTT assay. Results Five targeted compounds were designed and synthesized, and their chemical structures were confirmed by ¹H-NMR and ESI-MS. The cell test results in vitro showed that all these compounds were more sensitive to S180 and H22 cells, and were less toxic to normal cells L929. The activities of some compounds were higher than positive control drug doxorubicin. Conclusion The targeted compounds have good antitumor activities in vitro, and compound 2b is considered to be a promising candidate.