Water-Soluble Gold(III)–Metformin Complex Alters Mitochondrial Bioenergetics in Breast Cancer Cells |
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Authors: | Dr Jong Hyun Kim Samuel Ofori R Tyler Mertens Prof Sean Parkin Prof Samuel G Awuah |
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Affiliation: | Department of Chemistry, University of Kentucky, 505 Rose Street, Lexington, KY 40506 USA |
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Abstract: | Chemical control of mitochondrial dynamics and bioenergetics can unravel fundamental biological mechanisms and therapeutics for several diseases including, diabetes and cancer. We synthesized stable, water-soluble gold(III) complexes (Auraformin) supported by biguanide metformin or phenylmetformin for efficacious inhibition of mitochondrial respiration. The new compounds were characterized following the reaction of C N]-cyclometalated gold(III) compounds with respective biguanides. Auraformin is solution stable in a physiologically relevant environment. We show that auraformin decreases mitochondrial respiration efficiently in comparison to the clinically used metformin by 100-fold. The compound displays significant mitochondrial uptake and induces antiproliferative activity in the micromolar range. Our results shed light on the development of new scaffolds as improved inhibitors of mitochondrial respiration. |
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Keywords: | Anticancer Gold(III)-Metformin Complexes Mitochondria Inhibition OXPHOS Auraformin |
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