新的依托泊苷衍生物作为细胞毒药物的设计, 合成和生物活性评价

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.

Design, Synthesis and Biological Evaluation of Novel Etoposide Analogues as Cytotoxic Agents

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.