Synthesis and antitumor activity of new glycosides of epipodophyllotoxin, analogues of etoposide, and NK 611
- J Med Chem. 1998 Nov 5;41(23):4475-85. doi: 10.1021/jm9800752.
- 1. UMR 176 CNRS/Institut Curie, Section Recherche, 26 rue d'Ulm, F-75248 Paris Cedex 05, France.
A series of 3-amino- and 3-alkylamino-2-deoxy-beta-D-ribo- and beta-D-arabino-glycosides of 4'-demethylepipodophyllotoxin have been synthesized by means of an improved trimethylsilyliodide procedure for the podophyllotoxin-4'-demethylepipodophyllotoxin conversion, an efficient and high yielding synthesis of silyl glycoside donors of 3-azido-2,3-dideoxy-beta-D-ribo- and beta-D-arabino-hexopyranosides and stereoselective glycosylations. In vitro evaluation of cytotoxic effects against murine L1210 leukemia critically demonstrates the essential role played by a 4,6-acetal for biological activity. Among the most cytotoxic compounds, 3-amino-2,3-dideoxy- and 3-N, N-(dimethylamino)-2,3-dideoxy etoposide analogues, 17 and 27-29 are at least as potent as etoposide on the in vivo P388 (iv/IP) murine leukemia models. However, surprisingly enough, none of these compounds inhibits the human DNA topoisomerases I or II or binds to tubulin to prevent its polymerization and microtubule assembly. Therefore, their mechanism of action remains to be cleared up.
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Cat. No.Product NameDescriptionTargetResearch Area
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Research Areas: Cancer