Issue 2, 2016

Targeting antioxidant pathways with ferrocenylated N-heterocyclic carbene supported gold(i) complexes in A549 lung cancer cells

Abstract

Ferrocene containing N-heterocyclic carbene (NHC) ligated gold(I) complexes of the type [Au(NHC)2]+ were prepared and found to be capable of regulating the formation of reactive oxygen species (ROS) via multiple mechanisms. Single crystal X-ray analysis of bis(1-(ferrocenylmethyl)-3-mesitylimidazol-2-ylidene)-gold(I) chloride (5) and bis(1,3-di(ferrocenylmethyl)imidazol-2-ylidene)-gold(I) chloride (6) revealed a quasi-linear geometry around the gold(I) centers (i.e., the C–Au–C bond angle were measured to be ∼177° and all the Au–Ccarbene bonds distances were in the range of 2.00 (7)–2.03 (1) Å). A series of cell studies indicated that cell proliferation inhibition and ROS generation were directly proportional to the amount of ferrocene contained within the [Au(NHC)2]+ complexes (IC50 of 6 < 5 < bis(1-benzyl-3-mesitylimidazol-2-ylidene)-gold(I) chloride (4)). Complexes 4–6 were also confirmed to inhibit thioredoxin reductase as inferred from lipoate reduction assays and increased chelatable intracellular zinc concentrations. RNA microarray gene expression assays revealed that 6 induces endoplasmic reticulum stress response pathways as a result of ROS increase.

Graphical abstract: Targeting antioxidant pathways with ferrocenylated N-heterocyclic carbene supported gold(i) complexes in A549 lung cancer cells

Supplementary files

Article information

Article type
Edge Article
Submitted
17 Sep 2015
Accepted
28 Oct 2015
First published
29 Oct 2015
This article is Open Access

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

Chem. Sci., 2016,7, 1245-1256

Author version available

Targeting antioxidant pathways with ferrocenylated N-heterocyclic carbene supported gold(I) complexes in A549 lung cancer cells

J. F. Arambula, R. McCall, K. J. Sidoran, D. Magda, N. A. Mitchell, C. W. Bielawski, V. M. Lynch, J. L. Sessler and K. Arumugam, Chem. Sci., 2016, 7, 1245 DOI: 10.1039/C5SC03519H

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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