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

Gold(III) pyridine-benzimidazole complexes as aquaglyceroporin inhibitors and antiproliferative agents
Gold(III) pyridine-benzimidazole complexes as aquaglyceroporin inhibitors and antiproliferative agents
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.
Gold(III) complexes, pyridine benzimidazole, aquaporins, cancer, stopped-flow spectroscopy, antiproliferative activity
1-16
Aikman, Brech
e117e4cb-1bde-4c8c-bcf7-c975e8972cc6
Wenzel, Margot N.
4c0522d1-7454-4cbf-8bc4-c220a822ff0b
Mósca, Andreia F.
922019e4-8329-4cdd-b6a6-6bece4e1bb23
de Almeida, Andreia
ac4a4939-43a1-4aa4-9629-cca25e48c258
Klooster, Wim
64dc0111-f415-4226-9189-45764c0933d9
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Soveral, Graça
efebc226-e0e0-421f-a353-cafef3b53a9e
Casini, Angela
27012a50-6e79-4b89-b843-c813b358f332
Aikman, Brech
e117e4cb-1bde-4c8c-bcf7-c975e8972cc6
Wenzel, Margot N.
4c0522d1-7454-4cbf-8bc4-c220a822ff0b
Mósca, Andreia F.
922019e4-8329-4cdd-b6a6-6bece4e1bb23
de Almeida, Andreia
ac4a4939-43a1-4aa4-9629-cca25e48c258
Klooster, Wim
64dc0111-f415-4226-9189-45764c0933d9
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Soveral, Graça
efebc226-e0e0-421f-a353-cafef3b53a9e
Casini, Angela
27012a50-6e79-4b89-b843-c813b358f332

Aikman, Brech, Wenzel, Margot N., Mósca, Andreia F., de Almeida, Andreia, Klooster, Wim, Coles, Simon J., Soveral, Graça and Casini, Angela (2018) Gold(III) pyridine-benzimidazole complexes as aquaglyceroporin inhibitors and antiproliferative agents. Inorganics, 6 (4), 1-16. (doi:10.3390/inorganics6040123).

Record type: Article

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.

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Accepted/In Press date: 15 November 2018
e-pub ahead of print date: 20 November 2018
Published date: 20 November 2018
Keywords: Gold(III) complexes, pyridine benzimidazole, aquaporins, cancer, stopped-flow spectroscopy, antiproliferative activity

Identifiers

Local EPrints ID: 426867
URI: https://eprints.soton.ac.uk/id/eprint/426867
PURE UUID: c7f916cf-bbd4-42dc-b29e-13c76c30facb
ORCID for Simon J. Coles: ORCID iD orcid.org/0000-0001-8414-9272

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Date deposited: 14 Dec 2018 17:30
Last modified: 14 Mar 2019 01:48

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Contributors

Author: Brech Aikman
Author: Margot N. Wenzel
Author: Andreia F. Mósca
Author: Andreia de Almeida
Author: Wim Klooster
Author: Simon J. Coles ORCID iD
Author: Graça Soveral
Author: Angela Casini

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