Cytotoxicity of acridinium-based ionic liquids: Structure-activity relationship and mechanistic studies.

Roy, R; Chick, P; York, E; Rawling, T

Cytotoxicity of acridinium-based ionic liquids: Structure-activity relationship and mechanistic studies.

Roy, R Chick, P York, E Rawling, T

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Publisher:: ELSEVIER IRELAND LTD
Publication Type:: Journal Article
Citation:: Chem Biol Interact, 2024, 396, pp. 111042
Issue Date:: 2024-06-01

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Field	Value	Language
dc.contributor.author	Roy, R
dc.contributor.author	Chick, P
dc.contributor.author	York, E
dc.contributor.author	Rawling, T https://orcid.org/0000-0002-6624-6586
dc.date.accessioned	2024-12-12T01:09:08Z
dc.date.available	2024-05-05
dc.date.available	2024-12-12T01:09:08Z
dc.date.issued	2024-06-01
dc.identifier.citation	Chem Biol Interact, 2024, 396, pp. 111042
dc.identifier.issn	0009-2797
dc.identifier.issn	1872-7786
dc.identifier.uri	http://hdl.handle.net/10453/182486
dc.description.abstract	Ionic liquids (ILs) are a class of low melting point salts with physicochemical properties suitable for a range of industrial applications such as chemical processing and battery design. Major challenges to the wide-scale adoption of ILs in industry include their eco- and cytotoxic effects, however, this opens up the possibility of the use of ILs use as novel anticancer agents. Understanding the structural features that promote IL cytotoxicity is therefore important. Key structural features that can impact IL cytotoxicity include size and lipophilicity of the cationic head group. In this study, the cytotoxic effects of acridinium-based ILs containing relatively large tri- and tetracyclic cations were evaluated. It was found that 9-phenylacridinium-based ILs are potent cytotoxic agents that reduce the viability of human MDA-MB-231 breast cancer cells with IC50 concentrations in the nanomolar range. In mechanistic studies, it was found that unlike the pyridinium-based analogue, [C16Py][I], acridinium-based ILs did not inhibit oxidative phosphorylation or induce reactive oxygen species formation, and may instead target other mitochondrial processes or components such as mitochondrial DNA.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	ELSEVIER IRELAND LTD
dc.relation.ispartof	Chem Biol Interact
dc.relation.isbasedon	10.1016/j.cbi.2024.111042
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology
dc.subject.classification	Toxicology
dc.subject.classification	3101 Biochemistry and cell biology
dc.subject.mesh	Humans
dc.subject.mesh	Ionic Liquids
dc.subject.mesh	Acridines
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Reactive Oxygen Species
dc.subject.mesh	Cell Survival
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Oxidative Phosphorylation
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Humans
dc.subject.mesh	Reactive Oxygen Species
dc.subject.mesh	Acridines
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Cell Survival
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Oxidative Phosphorylation
dc.subject.mesh	Ionic Liquids
dc.subject.mesh	Humans
dc.subject.mesh	Ionic Liquids
dc.subject.mesh	Acridines
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Reactive Oxygen Species
dc.subject.mesh	Cell Survival
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Oxidative Phosphorylation
dc.title	Cytotoxicity of acridinium-based ionic liquids: Structure-activity relationship and mechanistic studies.
dc.type	Journal Article
utslib.citation.volume	396
utslib.location.activity	Ireland
utslib.for	0601 Biochemistry and Cell Biology
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2024-12-12T01:09:07Z
pubs.publication-status	Published
pubs.volume	396

Abstract:

Ionic liquids (ILs) are a class of low melting point salts with physicochemical properties suitable for a range of industrial applications such as chemical processing and battery design. Major challenges to the wide-scale adoption of ILs in industry include their eco- and cytotoxic effects, however, this opens up the possibility of the use of ILs use as novel anticancer agents. Understanding the structural features that promote IL cytotoxicity is therefore important. Key structural features that can impact IL cytotoxicity include size and lipophilicity of the cationic head group. In this study, the cytotoxic effects of acridinium-based ILs containing relatively large tri- and tetracyclic cations were evaluated. It was found that 9-phenylacridinium-based ILs are potent cytotoxic agents that reduce the viability of human MDA-MB-231 breast cancer cells with IC50 concentrations in the nanomolar range. In mechanistic studies, it was found that unlike the pyridinium-based analogue, [C16Py][I], acridinium-based ILs did not inhibit oxidative phosphorylation or induce reactive oxygen species formation, and may instead target other mitochondrial processes or components such as mitochondrial DNA.

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http://hdl.handle.net/10453/182486