Synthesis and stability evaluation of 5-FU-acetic podophyllic ester as anti-tumor agent

5-FU-乙酸鬼臼酯的合成及稳定性研究(英文)

Aim To study a new anti-cancer drug 5-FU-acetic podophyllic ester derivatized from podophyllotoxin. Methods A novel derivative of podophyllotoxin was synthesized. Its inhibitory effects against P-388, A-549, Bel-7402 and HL-60 in vitro were tested. The stability tests under different kinds of conditions were carried out. Results The novel derivative showed stronger inhibitory activities against P-388, A-549 and Bel-7402 in vitro than VP-16. The novel derivative was found to be stable at 60 ℃ and 4500 1x light in solid-state, but was less stable in humid condition. It was more stable in methanol （4 ℃ ） and chloroform （25 ℃ ） than in methanol （25 ℃）, and less stable in artificial gastric juice （ AGJ, 37 ℃ ）. Its stabilities were decreased while increasing the pH of buffer solutions. Conclusion These results could provide useful information for further study of this compound.

目的研究一种新型鬼臼类抗肿瘤药物。方法根据拼合原理合成一种新的鬼臼类似物,并测定了其体外对肿瘤细胞的活性及在多种介质中的稳定性。结果合成的化合物在体外对P-388,A-549和Bel-7402肿瘤细胞表现出比 VP-16更强的抑制活性。同时固体样品对温度、光等因素的改变较稳定, 而在人工胃液(AGJ)及pH较高的缓冲溶液中和高湿度条件下稳定性较差。结论本试验的结果为该化合物的进一步研究提供了研究基础。