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 microM, 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 cytotoxicity and antioxidative activity discussed.
Jin
Yan
Y
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China.
Chen
Shi-Wu
SW
Tian
Xuan
X
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D011034:Podophyllotoxin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000975:Antioxidants; D011034:Podophyllotoxin