Synthesis and biological evaluation of new spin-labeled derivatives of podophyllotoxin

In order to find compounds with superior bioactivity and less toxicity, a series of spin-labeled podophyllotoxin derivatives were synthesized and tested for the partition coefficients and cytotoxicity against P-388 and A-549. Furthermore, we also determined antioxidant activities of target molecular in tissues of SD rats by the TBA method. Results revealed that most synthesized compounds showed more significant cytotoxicity against P-388 and A-549 in vitro than VP-16. Among them, 9d exhibited most potent cytotoxicity against P-388 and A-549 cells (IC50 is <0.01 and 0.13 μM, respectively). Also, the antioxidative activities showed that the modified compounds of 4′-demethylepipodophyllotoxin (9a–d and 10a–c) are higher than those of podophyllotoxin series (8a–d). The relationship between the cytotoxity and antioxidative activity discussed.

Target compounds with 4β-stable nitroxides and (or) 4′-hydroxyl ester showed generally superior cytotoxicities than VP-16, and their antioxidative activities were in accord with antitumor activities.Figure optionsDownload as PowerPoint slide