Design and Synthesis of N-phosphoryl Peptide Modified Podophyllotoxin Derivatives as Potent Anticancer Agents

A series of novel compounds with N-phosphoryl peptide modification at the C-4 position on podophyllotoxin were synthesized and evaluated for their cytotoxicity in vitro against K562 cell lines. Among these compounds 5c, 5f and 5k exhibited better cytotoxicity (IC50 = 5.5 mu M, 2.1 mu M, and 3.1 mu M, respectively) than podophyllotoxin and etoposide. Further study on compound 5f using flow cytometry analysis indicated that the anti-tumor effect might be due to the induction of apoptosis.