New spin labeled analogues of podophyllotoxin as potential antitumor agents.
Four new nitroxyl labeled derivatives of podophyllotoxin, 4-(2, 2, 6, 6-tetramethyl-1-oxyl-4-piperidyl)oxy-epipodophyllotoxin (4), 4-(2, 2, 6, 6-tetramethyl-1-oxyl-4-piperidyl)oxy-4'-demethylepipodophyllotoxin (5), 4-(2, 2, 5, 5-tetramethyl-1-oxyl-3-pyrrolinyl)formyloxy-epipodophyllotox in (6) and 4-(2, 2, 5, 5-tetramethyl-1-oxyl-3-pyrrolinyl)formyloxy-4'-demethylep ipodophyllotoxin (7), have been synthesized and evaluated for their antitumor activity in vitro. Compounds 5 and 7 showed superior activity to clinically used etoposide (VP-16,2) in their inhibition of leukemia P388, lung cancer A549 and stomach carcinoma SGC-7901 cells. 4'-Demethyl-epipodophyllotoxins 5 and 7 was found to be more active than eipodophyllotoxins 4 and 6 lacking a free phenolic hydroxyl group at C-4'.
Wang
Y
Y
Department of Chemistry, Zhejiang University, Hangzhou, P.R. China.
Pan
J
J
Shi
J
J
Chen
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008956:Models, Chemical; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013113:Spin Labels; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D013113:Spin Labels; D011034:Podophyllotoxin