Gold(III) pyridine-benzimidazole complexes as aquaglyceroporin inhibitors and antiproliferative agents

Brech Aikman, Margot N. Wenzel, Andreia F. Mósca, Andreia de Almeida, Wim T. Klooster, Simon J. Coles, Graça Soveral, Angela Casini

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Gold compounds have been proven to be novel and versatile tools for biological applications, including as anticancer agents. Recently, we explored the potential of Au(III) complexes with bi-dentate N-donor ligands as inhibitors of the membrane water and glycerol channels aquaporins (AQPs), involved in different physiological and pathophysiological pathways. Here, eight new Au(III) complexes featuring a pyridine-benzimidazole scaffold have been synthesized and characterized via different methods. The stability of all the compounds in aqueous solution and their reactivity with glutathione have been investigated by UV-visible spectroscopy. The Au(III) compounds, tested for their AQPs inhibition properties in human Red Blood Cells (hRBC), are potent and selective inhibitors of AQP3. Furthermore, the compounds' antiproliferative effects have been studied in a small panel of human cancer cells expressing AQP3. The complexes show only very moderate anticancer effects in vitro and are mostly active against the melanoma A375 cells, with marked expression of AQP3 at the level of the nuclear membrane. In general, the AQP3 inhibition properties of these complexes hold promises to develop them as chemical probes to study the function of this protein isoform in biological systems.

Original languageEnglish
Article number123
JournalInorganics
Volume6
Issue number4
DOIs
StatePublished - 1 Dec 2018
Externally publishedYes

Keywords

  • Antiproliferative activity
  • Aquaporins
  • Cancer
  • Gold(III) complexes
  • Pyridine benzimidazole
  • Stopped-flow spectroscopy

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