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

Abstract

In order to find novel synthetic compounds with superior antitumor activity and overcome multidrug resistance, a series of novel 4β-N-substituted podophyllotoxin derivatives were synthesized under mild conditions with satisfactory yield. Nine novel podophyllotoxin derivatives were synthesized by linking 4β-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.

Keywords::

• podophyllotoxin derivatives
• antitumor
• multidrug resistance

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (No. 30873363), Program of Science Foundation of Tianjin (08JCYBJC070000), and Major Program of Science Foundation of Tianjin (09ZCKFSH01700).