Doxorubicin-antioxidant co-drugs

Bioorg Med Chem Lett. 2013 Oct 1;23(19):5307-10. doi: 10.1016/j.bmcl.2013.07.070. Epub 2013 Aug 8.

Abstract

Doxorubicin-antioxidant multitarget compounds 6 and 7 were obtained by combining doxorubicin (DOX) with caffeic and ferulic acids through an ester linkage at C-14. The products were studied in in vitro models of cardiomyocytes and breast cancer cells, characterized by different degrees of resistance to DOX, due to different expressions of ATP binding cassette (ABC) transporters. Compound 7 was found to be less toxic than DOX in cardiomyocytes and to display the same possibly higher toxicity against the resistant breast cancer cells. This result shows that appropriate DOX-antioxidant co-drugs can limit the onset of cardiac damage, a significant side-effect of DOX, without impairing the antitumor activity of the parent antibiotic.

Keywords: ABC transporters; Antioxidant; Cardiotoxicity; Doxorubicin; Ferulic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Resistance, Multiple / drug effects
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Molecular Structure
  • Myocytes, Cardiac / drug effects

Substances

  • Antioxidants
  • Doxorubicin