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

Abstract

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 (IC 50 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.