目的 設計合成苯氧基磷酰氮芥取代的槐定堿衍生物，并對其進行體外抗腫瘤活性研究。方法 以槐定堿為起始原料，經(jīng)開環(huán)、酯化、磷?；确磻铣赡繕嘶衔?b>2a ～2e ，采用MTT法測定其對S180、H22、K562、MCF-7、SMMC-7721、LoVo腫瘤細胞的抑制活性。結果 設計并合成了5個目標化合物，其結構經(jīng)¹H-NMR和ESI-MS確證。體外細胞測試結果顯示所有化合物對S180和H22細胞株活性較強，且對正常細胞L929毒性小，部分化合物活性高于陽性對照藥多柔比星。結論 目標化合物具有較強的抗腫瘤活性，化合物2b 為有潛力的候選化合物。

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.

天津市自然科學基金資助項目（17JCQNJC13600）