Carminomycin, 14-hydroxycarminomycin and its novel carbohydrate derivatives potently kill human tumor cells and their multidrug resistant variants.

Abstract

The new hydrophilic derivatives of 14-hydroxycarminomycin were obtained using 13-dimethyl ketal of 14-bromocarminomycin (6) as the starting compound. The reductive alkylation of 6 with melibiose or D-galactose followed by hydrolysis of the corresponding intermediate bromoketals 9 and 11 produced 3'-N-[-alpha-D-(galactopyranosyl-(1 --> 6)-O-D-1-desoxyglucit-1-yl]-14-hydroxycarminomycin (10) and 3'-N-(1-desoxy-D-galactit-1-yl)-14-hydroxycarminomycin (12), respectively. These novel derivatives 10 and 12 were less toxic than carminomycin or 14-hydroxycarminomycin for leukemia (K562) and breast carcinoma (MCF-7) cells. Importantly, carminomycin, 14-hydroxycarminomycin and compounds 10 and 12 were similarly active for wild type cells and their multidrug resistant (MDR) sublines, K562i/S9 and MCF-7Dox.

• Authors: Anna N Tevyashova, Alexander A Shtil, Eugenia N Olsufyeva, Valeria S Simonova, Alexei V Samusenko, Maria N Preobrazhenskaya
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 57 Issue 2 Pg. 143-50 (Feb 2004) ISSN: 0021-8820 [Print] England
• PMID: 15112963 (Publication Type: Journal Article)

Chemical References

• 14-hydroxycarminomycin
• ATP Binding Cassette Transporter, Subfamily B
• Antibiotics, Antineoplastic
• Carubicin

Topics

• ATP Binding Cassette Transporter, Subfamily B (metabolism)
• Antibiotics, Antineoplastic (pharmacology)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Carubicin (analogs & derivatives, pharmacology)
• Cell Survival
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Drug Screening Assays, Antitumor
• Female
• Genes, MDR (genetics)
• Humans
• Leukemia (drug therapy, metabolism, pathology)
• Structure-Activity Relationship
• Tumor Cells, Cultured