RESUMO
The relationship between the structure of new semisynthetic derivatives of doxorubicin, daunorubicin, and carminomycin and their ability to inhibit topoisomerase 1 were studied. The new derivatives inhibit the activity of topoisomerase 1 at low concentrations, induce the death of K-562 leukemia cells in culture, and produce an antitumor effect in experimental animals with P388 leukemia.
Assuntos
Carrubicina/análogos & derivados , Carrubicina/química , Daunorrubicina/análogos & derivados , Daunorrubicina/química , Doxorrubicina/análogos & derivados , Doxorrubicina/química , Inibidores da Topoisomerase I , Animais , Carrubicina/farmacologia , Daunorrubicina/farmacologia , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células K562 , Leucemia P388/tratamento farmacológico , Camundongos , Relação Estrutura-AtividadeRESUMO
New water-soluble conjugates in the form of Schiff bases (DGM-1 and DGM-2) were prepared by the interaction of water-soluble periodate-oxidized galactomannan with doxorubicin or N-(L-lysyl)doxorubicin, respectively. The water-soluble galactomannan (DAVANAT a commercial product of Pro-Pharmaceuticals company) was obtained by partial acidic hydrolysis of high-molecular-mass galactomannan from Cyamopsis tetragonoloba (guar gum) seeds. The conjugate stability was studied in aqueous solutions. The DGM-1 antiproliferative activity was comparable with that of doxorubicin on three models: cell lines of murine melanoma B 16-F1, human breast cancer MCF-7 (HTB-22), and human colon cancer HT-29 (HTB-38). DGM-2 was poorly active in all the three tests. DGM- 1 can thus be regarded as a high-molecular-mass depot form of doxorubicin.
