Synthesis, biological and biochemical properties of new anthracyclines modified in the aminosugar moiety.
New 4'-C-methyl analogues of daunorubicin, synthesized by the coupling reaction of daunomycinone with 1-chloroderivatives of protected 4-C-methyldaunosamine analogues, were chemically transformed to the corresponding doxorubicin analogues. Their cytotoxic effect against HeLa cells, ability to bind to DNA, and in vivo toxicity and antitumor activity were compared with those of daunorubicin, doxorubicin, and their 4'-O-methyl analogues. The cytotoxic effect of the new anthracyclines could be correlated with their ability to bind to DNA and with their toxicity in experimental animals; however, the antitumor effectiveness did not seem to be related to these parameters. In general all the compounds retained a remarkable antitumor activity at their optimal doses. The most active compound against P388 leukemia was 4'-O-methyldoxorubicin, which was also more active than doxorubicin against L1210 leukemia.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000633:toxicity; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000633:toxicity; D006367:HeLa Cells / Q000378:metabolism; D006595:Hexosamines; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D009368:Neoplasm Transplantation; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D006595:Hexosamines; C007217:daunosamine; D004317:Doxorubicin; D004247:DNA; D003630:Daunorubicin