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

• 8-Hydroxyquinoline (OHQ) derivatives are cytotoxic compounds.
• 8-OHQ derivatives are ionophores of transition metal ions.
• High levels of copper have been found in many types of human cancers.
• New galactoconjugates of 8-OHQ activated by β-galactosidases were synthesized.

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.

We designed new galactoconjugates of 8-hydroxyquinolines activable by β-galactosidase. For some of them the presence of copper(II) ions determines a pharmacologically relevant antiproliferative activity against specific tumor cells. The antiproliferative activity of the galactoconjugates increases in the presence of β-galactosidase suggesting their suitability for enzyme-activated prodrug therapies.Figure optionsDownload as PowerPoint slide