Issue 21, 2021

Anticancer gold(iii)-bisphosphine complex alters the mitochondrial electron transport chain to induce in vivo tumor inhibition

Abstract

Expanding the chemical diversity of metal complexes provides a robust platform to generate functional bioactive reagents. To access an excellent repository of metal-based compounds for probe/drug discovery, we capitalized on the rich chemistry of gold to create organometallic gold(III) compounds by ligand tuning. We obtained novel organogold(III) compounds bearing a 1,2-bis(diphenylphosphino)benzene ligand, providing structural diversity with optimal physiological stability. Biological evaluation of the lead compound AuPhos-89 demonstrates mitochondrial complex I-mediated alteration of the mitochondrial electron transport chain (ETC) to drive respiration and diminish cellular energy in the form of adenosine triphosphate (ATP). Mechanism-of-action efforts, RNA-Seq, quantitative proteomics, and NCI-60 screening reveal a highly potent anticancer agent that modulates mitochondrial ETC. AuPhos-89 inhibits the tumor growth of metastatic triple negative breast cancer and represents a new strategy to study the modulation of mitochondrial respiration for the treatment of aggressive cancer and other disease states where mitochondria play a pivotal role in the pathobiology.

Graphical abstract: Anticancer gold(iii)-bisphosphine complex alters the mitochondrial electron transport chain to induce in vivo tumor inhibition

Supplementary files

Article information

Article type
Edge Article
Submitted
10 Mar 2021
Accepted
16 Apr 2021
First published
29 Apr 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2021,12, 7467-7479

Anticancer gold(III)-bisphosphine complex alters the mitochondrial electron transport chain to induce in vivo tumor inhibition

J. H. Kim, S. Ofori, S. Parkin, H. Vekaria, P. G. Sullivan and S. G. Awuah, Chem. Sci., 2021, 12, 7467 DOI: 10.1039/D1SC01418H

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements