Synthesis And Biological Evaluation Of Conjugates Of Deoxypodophyllotin And5-FU

Deoxypodophyllotoxin has antiproliferative and antitumor activity, anti-inflammatory and anti-viral activity. In order to generate compounds with superior antitumor activity and reduced toxicity, a serried of conjugates of deoxypodophyllotoxin and5-FU were synthesized by coupling4’-demethyl-4-dexoypodophyllotoxin with N-(5-fluorouracil-N’-ly acetic)-amino acids (or5-fluorouracil-N’-ly acetic acid). The cytotoxic activity of these compounds against four human cancer cell lines (HL-60, A-549, HeLa and SiHa) were evaluated, and results indicated that these compounds were more potent in terms of cytotoxicity than either parent compound DPT or anticancer drug VP-16and5-FU. In addition, we found that14d induced cell cycle arrest in the G2/M phase accompanied by apoptosis in A-549cells, and7d activated caspase-3and-7. These results suggested that caspase-mediated pathways are involved in7d induced apoptosis.