RESUMO
The synthesis of four new ethers of daunorubicin, namely 6-, 9-, 11-monomethyl and 6,9-dimethyl, along with the 4'-methyl ethers of 11-deoxydaunorubicin and 11-deoxydoxorubicin is reported. While the methylation of any of the mentioned hydroxyl groups of the aglycone moiety of daunorubicin resulted in a practically complete loss of bioactivity, the methylation of the aminosugar hydroxyl group of 11-deoxydaunorubicin and 11-deoxydoxorubicin increased their effectiveness on P 388 leukemia in mice.
Assuntos
Daunorrubicina/análogos & derivados , Animais , Antibióticos Antineoplásicos , Daunorrubicina/síntese química , Daunorrubicina/farmacologia , Daunorrubicina/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Leucemia P388/tratamento farmacológico , Metilação , Camundongos , Naftacenos/síntese química , Naftacenos/farmacologia , Naftacenos/uso terapêuticoRESUMO
Four glycosides, designated A, B, C and D, are the main components of the anthracycline complex produced by cultures of Micromonospora sp. nov. They were extracted by solvent partition, separated by column chromatography and characterized by chemical and physical methods as 11-deoxy analogues of daunorubicin. Among these new anthracyclines, displaying antibacterial and cytotoxic activity in vitro, 11-deoxydaunorubicin and 11-deoxydoxorubicin are also active against P388 leukemia in mice.