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Open AccessArticle

Gold(III) Pyridine-Benzimidazole Complexes as Aquaglyceroporin Inhibitors and Antiproliferative Agents

1
School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, UK
2
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal
3
Tumour MicroEnvironment Group, Division of Cancer and Genetics, School of Medicine, Cardiff University, Tenovus Building, Cardiff CF14 4XN, UK
4
School of Chemistry, University of Southampton, Southampton SO17 1BJ, UK
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Inorganics 2018, 6(4), 123; https://doi.org/10.3390/inorganics6040123
Received: 11 October 2018 / Revised: 14 November 2018 / Accepted: 15 November 2018 / Published: 20 November 2018
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. View Full-Text
Keywords: Gold(III) complexes; pyridine benzimidazole; aquaporins; cancer; stopped-flow spectroscopy; antiproliferative activity Gold(III) complexes; pyridine benzimidazole; aquaporins; cancer; stopped-flow spectroscopy; antiproliferative activity
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MDPI and ACS Style

Aikman, B.; Wenzel, M.N.; Mósca, A.F.; De Almeida, A.; Klooster, W.T.; Coles, S.J.; Soveral, G.; Casini, A. Gold(III) Pyridine-Benzimidazole Complexes as Aquaglyceroporin Inhibitors and Antiproliferative Agents. Inorganics 2018, 6, 123.

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