Water-Soluble Gold(III)–Metformin Complex Alters Mitochondrial Bioenergetics in Breast Cancer Cells

Jong Hyun Kim, Samuel Ofori, R. Tyler Mertens, Sean Parkin, Samuel G. Awuah

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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.

Original languageEnglish
Pages (from-to)3222-3230
Number of pages9
JournalChemMedChem
Volume16
Issue number20
DOIs
StatePublished - Oct 15 2021

Bibliographical note

Publisher Copyright:
© 2021 Wiley-VCH GmbH.

Keywords

  • Anticancer
  • Auraformin
  • Gold(III)-Metformin Complexes
  • Mitochondria Inhibition
  • OXPHOS

ASJC Scopus subject areas

  • Drug Discovery
  • General Pharmacology, Toxicology and Pharmaceutics
  • Molecular Medicine
  • Biochemistry
  • Pharmacology
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Water-Soluble Gold(III)–Metformin Complex Alters Mitochondrial Bioenergetics in Breast Cancer Cells'. Together they form a unique fingerprint.

Cite this