摘要：Five novel compounds composed of etoposide and 5-fluorouracil derivatives joined by an ester linkage were prepared and evaluated for their antitumor potential. Most of these analogues have exhibited promising in vitro cytotoxic activity against cell cultures of murine leukaemia P-388 and human lung carcinoma A-549. The results presented herein challenged the long-standing structure-activity relationships, which proposed that a free 4＇-hydroxyl group is essential structural requirement for etoposide-like activity. And in addition, the 4＇-position was suggested to tolerate chemical modifications such as esterification. The preliminary testing results also indicated that the design and synthesis of these compounds were beneficial for therapeutic values of etoposide.

摘要：目的采用复合磷脂制备5-氟尿嘧啶(5-fluorouracil,5-FU)长循环脂质体,进行处方和工艺优化,并建立初步表征评价。方法采用逆向蒸发法制备5-FU复合磷脂长循环脂质体,用聚乙二醇(DSPE-mPEG2000)修饰脂质体,并根据单因素试验考察复合磷脂的比例、磷脂与胆固醇比例、药脂比、外水相pH值、载药温度及时间对5-FU长循环脂质体包封率的影响。采用紫外分光光度法测定包封率,以包封率为指标,分别考察蛋黄卵磷脂(E80)/氢化大豆磷脂(hydrogenated soy phosphatidylcholine,HSPC)质量比、药脂比、磷脂/胆固醇质量比以及外水相缓冲液pH等因素对脂质体质量的影响,在此基础上用正交设计对处方进行优化。考察5-氟尿嘧啶长循环脂质体的制剂学性质以及脂质体在4℃冷藏条件下的30天样品稳定性。结果经逆向蒸发法制备的5-FU长循环脂质体包封率为(68.81±0.22)%,载药量为(5.47±0.02)%。电镜结果及粒径检测显示,平均粒径为107 nm左右,PDI值稳定在0.3以下,粒度分布均匀,且呈单峰分布。于4℃条件放置3 d包封率无明显变化,30 d包封率下降(2.86±0.21)%。结论用复合磷脂制备的5-FU长循环脂质体制备工艺简单可行,性质稳定。