Synthesis and antitumor properties of new glycosides of daunomycinone and adriamycinone.
The synthesis of 4'-epi-daunorubicin and of 4'-epi-adriamycin was performed by condensation of 2,3,6-trideoxy-3-trifluoroacetamido-4-O-trifluoroacetyl-alpha-L-arabino-hexopyranosyl chloride with daunomycinone or the protected adriamycinone derivative 17, respectively. Both the alpha and beta anomers were obtained and characterized. All new compounds are biologically active in cultured cells and the alpha anomers display noticeable activity in experimental tumors in mice. Interestingly, 4'-epi-adriamycin (4) appears nontoxic to cultured heart cells up to a concentration of 5 mug/ml.
D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D006367:HeLa Cells / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D008979:Moloney murine leukemia virus / Q000187:drug effects; D012510:Sarcoma 180 / Q000188:drug therapy; D009053:Sarcoma Viruses, Murine / Q000187:drug effects; D013237:Stereoisomerism
D000617:Aminoglycosides; D000970:Antineoplastic Agents; D004317:Doxorubicin; D003630:Daunorubicin