New 8-hydroxyquinoline galactosides. The role of the sugar in the antiproliferative activity of copper(II) ionophores

J Inorg Biochem. 2015 Jan:142:101-8. doi: 10.1016/j.jinorgbio.2014.09.017. Epub 2014 Oct 17.

Abstract

8-Hydroxyquinoline derivatives and their metal complexes have recently awakened interest as promising therapeutic agents in cancer therapy. We have previously synthesized and evaluated glucoconjugated 8-hydroxyquinolines as copper ionophores activated by β-glucosidases. In order to further evaluate the crucial role of the sugar, we designed and synthesized a series of new galactoconjugates of 8-hydroxyquinolines and investigated their biological properties in comparison with the 8-hydroxyquinoline analogs. The effect of copper(II) ions on their biological activities was evaluated. In particular, two compounds possess a pharmacologically relevant antiproliferative activity against specific tumor cells in the presence of copper(II) ions. Furthermore, the antiproliferative activity of the selected galactosides was successfully investigated in the presence of β-galactosidase as a preliminary model of antibody directed enzyme prodrug therapy.

Keywords: ADEPT; Clioquinol; Copper; Galactoside; Ionophore.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Cell Proliferation / drug effects*
  • Copper*
  • Drug Screening Assays, Antitumor
  • Hep G2 Cells
  • Humans
  • Ionophores* / chemical synthesis
  • Ionophores* / chemistry
  • Ionophores* / pharmacology
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Oxyquinoline / analogs & derivatives*
  • Oxyquinoline / chemical synthesis
  • Oxyquinoline / chemistry
  • Oxyquinoline / pharmacology

Substances

  • Ionophores
  • 8-hydroxyquinoline glucoside
  • Oxyquinoline
  • Copper