Novel anthracycline oligosaccharides: influence of chemical modifications of the carbohydrate moiety on biological activity

Bioorg Med Chem. 2002 May;10(5):1459-70. doi: 10.1016/s0968-0896(01)00411-4.

Abstract

Several observations highlight the importance of the carbohydrate moiety for the biological activity of antitumoural anthracyclines. Here is reported the synthesis, cytotoxicity and topoisomerase II-mediated DNA cleavage intensity of the new oligosaccharide anthracyclines 1--4 modified in the sugar residue. Evaluation of cytotoxic potency on different cell lines, resulted in quite similar values among the different analogues. On the other hand, topoisomerase II-mediated DNA breaks level was different for the various compounds, and was not related to cytotoxicity, thus supporting previous observations reported for some monosaccharide anthracyclines modified in the carbohydrate portion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / chemical synthesis*
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology
  • Carbohydrates / chemistry
  • Cell Survival / drug effects
  • DNA / metabolism
  • DNA Topoisomerases, Type II / drug effects
  • DNA Topoisomerases, Type II / pharmacology
  • Drug Screening Assays, Antitumor
  • Humans
  • Oligosaccharides / chemical synthesis
  • Oligosaccharides / chemistry
  • Oligosaccharides / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured / drug effects

Substances

  • Antibiotics, Antineoplastic
  • Carbohydrates
  • Oligosaccharides
  • DNA
  • DNA Topoisomerases, Type II