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

J Antibiot (Tokyo). 2004 Feb;57(2):143-50. doi: 10.7164/antibiotics.57.143.

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.

MeSH terms

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

Substances

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