Structure-Activity Relationship and Mitochondrial Actions of Ionic Liquids as Potential Anticancer Agents

Roy, Ritik

Structure-Activity Relationship and Mitochondrial Actions of Ionic Liquids as Potential Anticancer Agents

Roy, Ritik

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Publication Type:: Thesis
Issue Date:: 2023

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Field	Value	Language
dc.contributor.author	Roy, Ritik
dc.date.accessioned	2023-09-08T01:21:21Z
dc.date.available	2023-09-08T01:21:21Z
dc.date.issued	2023
dc.identifier.uri	http://hdl.handle.net/10453/171986
dc.description	University of Technology Sydney. Faculty of Science.	en_US.UTF-8
dc.description.abstract	Ionic liquids (ILs) are a class of low melting point salts. They possess unique physicochemical properties that make them amenable to many industrial processes, however, their cytotoxicity presents a liability for their commercial utilisation. On the other hand, the cytotoxicity of ILs presents opportunities for the development of novel anticancer agents. For these reasons, a well-defined structure-activity relationship (SAR) describing IL anticancer activity is important, however the current SAR is limited due in part to the low structural diversity of reported ILs. One of the aims of this project was to expand the SAR of ILs by assessing the impact of cationic head group structure on cytotoxicity. To address the aim, over 39 structurally diverse ILs were synthesised and their antiproliferative activity was assessed against human MDA-MB-231 breast cancer cells. Head group size and lipophilicity were found to increase cytotoxicity. Representative ILs were then selected for mechanistic studies, which indicated that ILs with planar, polycyclic cations may target mitochondrial DNA to induce cell death. ILs with non-intercalating cations targeted the inner mitochondrial membrane to induce mitochondrial dysfunction. Taken together, these insights may be used to develop ILs as either non-toxic industrial solvents or as cytotoxic agents with improved anticancer activity.	en_US.UTF-8
dc.format	Thesis (PhD)
dc.language.iso	en_US	en_US.UTF-8
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/171986/1/thesis.pdf
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	© 2023 Ritik Roy
dc.rights	au.edu.uts.lib/cph
dc.title	Structure-Activity Relationship and Mitochondrial Actions of Ionic Liquids as Potential Anticancer Agents	en_US.UTF-8
dc.type	Thesis
utslib.copyright.status	open_access	*

Abstract:

Ionic liquids (ILs) are a class of low melting point salts. They possess unique physicochemical properties that make them amenable to many industrial processes, however, their cytotoxicity presents a liability for their commercial utilisation. On the other hand, the cytotoxicity of ILs presents opportunities for the development of novel anticancer agents. For these reasons, a well-defined structure-activity relationship (SAR) describing IL anticancer activity is important, however the current SAR is limited due in part to the low structural diversity of reported ILs. One of the aims of this project was to expand the SAR of ILs by assessing the impact of cationic head group structure on cytotoxicity. To address the aim, over 39 structurally diverse ILs were synthesised and their antiproliferative activity was assessed against human MDA-MB-231 breast cancer cells. Head group size and lipophilicity were found to increase cytotoxicity. Representative ILs were then selected for mechanistic studies, which indicated that ILs with planar, polycyclic cations may target mitochondrial DNA to induce cell death. ILs with non-intercalating cations targeted the inner mitochondrial membrane to induce mitochondrial dysfunction. Taken together, these insights may be used to develop ILs as either non-toxic industrial solvents or as cytotoxic agents with improved anticancer activity.

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http://hdl.handle.net/10453/171986