Platinum-based metal complexes as chloride transporters that trigger apoptosis

Patrick Wang; Mohamed Fares; Radwa A. Eladwy; Deep J. Bhuyan; Xin Wu; William Lewis; Stephen J. Loeb; Lauren K. Macreadie; Philip A. Gale

doi:10.1039/D4SC02115K

Platinum-based metal complexes as chloride transporters that trigger apoptosis†

Patrick Wang,

^a Mohamed Fares,

^b Radwa A. Eladwy,^c Deep J. Bhuyan,

^c Xin Wu,

^d William Lewis,

^a Stephen J. Loeb,

^e Lauren K. Macreadie

^f and Philip A. Gale

*^g

Author affiliations

* Corresponding authors

^a School of Chemistry, The University of Sydney, NSW 2006, Australia

^b School of Pharmacy, The University of Sydney, NSW 2006, Australia

^c NICM, Research Health Institute, Western Sydney University, NSW 2751, Australia

^d School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, Fujian, China

^e Department of Chemistry and Biochemistry, University of Windsor, Ontario, Canada

^f School of Chemistry, The University of New South Wales, NSW, Australia

^g School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Ultimo NSW 2007, Australia
E-mail: philip.gale@uts.edu.au

Abstract

In this paper we demonstrate that Pt(II) complexes can function as efficient transmembrane chloride transporters. A series of Pt(II) metal complexes with urea-appended isoquinoline ligands were synthesised and operate via classical hydrogen bonding interactions rather than ligand exchange. A number of the complexes exhibited potent transmembrane chloride activity in vesicle studies, while also showing strong antiproliferative activity in cisplatin-resistant cell lines via induction of apoptosis and inhibition of intracellular ROS.

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DOI: https://doi.org/10.1039/D4SC02115K
Article type: Edge Article
Submitted: 01 Apr 2024
Accepted: 21 Jun 2024
First published: 26 Jun 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry

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Chem. Sci., 2024,15, 11584-11593

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Platinum-based metal complexes as chloride transporters that trigger apoptosis

P. Wang, M. Fares, R. A. Eladwy, D. J. Bhuyan, X. Wu, W. Lewis, S. J. Loeb, L. K. Macreadie and P. A. Gale, Chem. Sci., 2024, 15, 11584 DOI: 10.1039/D4SC02115K

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.

Chemical Science

Platinum-based metal complexes as chloride transporters that trigger apoptosis†

Abstract

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Platinum-based metal complexes as chloride transporters that trigger apoptosis

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