Design, synthesis, and antitumor activity of novel podophyllotoxin derivatives as potent anticancer agents

In order to find novel synthetic compounds with superior antitumor activity and overcome multidrug resistance, a series of novel 4-N-substituted podophyllotoxin derivatives were synthesized under mild conditions with satisfactory yield. Nine novel podophyllotoxin derivatives were synthesized by linking 4-amino-podophyllotoxin with aldehydes via the formation of a Schiff's base, and imines were reducted to secondary amines. These novel derivatives have been evaluated for cytotoxicity against human cancer cell lines Hela, K562, and K562/AO2. The results indicated that these compounds possess superior bioactivity (IC50 values were found at the range of 10(-6)-10(-8)mol/l) and weak multidrug resistance.