| Field |
Value |
Language |
|
dc.contributor.author |
Elmaghrabi, YA |
|
|
dc.contributor.author |
Roseblade, A |
|
|
dc.contributor.author |
Rahman, K |
|
|
dc.contributor.author |
Rawling, T
https://orcid.org/0000-0002-6624-6586
|
|
|
dc.contributor.author |
Murray, M |
|
|
dc.date.accessioned |
2025-01-30T05:09:35Z |
|
|
dc.date.available |
2025-01-30T05:09:35Z |
|
|
dc.date.issued |
2024-10-16 |
|
|
dc.identifier.citation |
ChemMedChem, 2024, 19, (20), pp. e202400281 |
|
|
dc.identifier.issn |
1860-7179 |
|
|
dc.identifier.issn |
1860-7187 |
|
|
dc.identifier.uri |
http://hdl.handle.net/10453/184640
|
|
|
dc.description.abstract |
The cancer cell mitochondrion could be a promising target for the development of new anticancer agents. 16-([3-chloro-5-(trifluoromethyl)-phenyl]carbamoylamino)hexadecanoic acid (2) is a novel aryl-urea fatty acid that targets the mitochondrion in MDA-MB-231 breast cancer cells and activates cell death. In the present study, the relationships between alkyl chain length in 2 analogues, mitochondrial disruption and cell killing were evaluated. The chain-contracted C13-analogue 7 c optimally disrupted the mitochondrial membrane potential (IC50 4.8±0.8 μM). In addition, annexin V-FITC/7-AAD assays demonstrated that 7 c was the most effective cell killing analogue and C11 BODIPY (581/591) assays demonstrated that 7 c was also most effective in generating reactive oxygen species in MDA-MB-231 cells. Together, carbon chain length is a key factor that determines the capacity of 2 analogues to disrupt the mitochondrial membrane, induce the production of reactive oxygen species and kill breast cancer cells. As an aryl-urea with enhanced activity and improved drug-like properties, 7 c may be a suitable lead molecule for entry into a program of development of these molecules as anticancer agents. |
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|
dc.format |
Print-Electronic |
|
|
dc.language |
eng |
|
|
dc.publisher |
WILEY-V C H VERLAG GMBH |
|
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dc.relation.ispartof |
ChemMedChem |
|
|
dc.relation.isbasedon |
10.1002/cmdc.202400281 |
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dc.rights |
info:eu-repo/semantics/openAccess |
|
|
dc.subject |
0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences |
|
|
dc.subject.classification |
Medicinal & Biomolecular Chemistry |
|
|
dc.subject.classification |
3404 Medicinal and biomolecular chemistry |
|
|
dc.subject.classification |
3405 Organic chemistry |
|
|
dc.subject.mesh |
Humans |
|
|
dc.subject.mesh |
Reactive Oxygen Species |
|
|
dc.subject.mesh |
Antineoplastic Agents |
|
|
dc.subject.mesh |
Mitochondria |
|
|
dc.subject.mesh |
Fatty Acids |
|
|
dc.subject.mesh |
Urea |
|
|
dc.subject.mesh |
Membrane Potential, Mitochondrial |
|
|
dc.subject.mesh |
Cell Line, Tumor |
|
|
dc.subject.mesh |
Structure-Activity Relationship |
|
|
dc.subject.mesh |
Drug Screening Assays, Antitumor |
|
|
dc.subject.mesh |
Molecular Structure |
|
|
dc.subject.mesh |
Cell Proliferation |
|
|
dc.subject.mesh |
Dose-Response Relationship, Drug |
|
|
dc.subject.mesh |
Carbon |
|
|
dc.subject.mesh |
Cell Survival |
|
|
dc.subject.mesh |
Cell Line, Tumor |
|
|
dc.subject.mesh |
Mitochondria |
|
|
dc.subject.mesh |
Humans |
|
|
dc.subject.mesh |
Carbon |
|
|
dc.subject.mesh |
Reactive Oxygen Species |
|
|
dc.subject.mesh |
Urea |
|
|
dc.subject.mesh |
Fatty Acids |
|
|
dc.subject.mesh |
Antineoplastic Agents |
|
|
dc.subject.mesh |
Drug Screening Assays, Antitumor |
|
|
dc.subject.mesh |
Cell Proliferation |
|
|
dc.subject.mesh |
Cell Survival |
|
|
dc.subject.mesh |
Molecular Structure |
|
|
dc.subject.mesh |
Structure-Activity Relationship |
|
|
dc.subject.mesh |
Dose-Response Relationship, Drug |
|
|
dc.subject.mesh |
Membrane Potential, Mitochondrial |
|
|
dc.subject.mesh |
Humans |
|
|
dc.subject.mesh |
Reactive Oxygen Species |
|
|
dc.subject.mesh |
Antineoplastic Agents |
|
|
dc.subject.mesh |
Mitochondria |
|
|
dc.subject.mesh |
Fatty Acids |
|
|
dc.subject.mesh |
Urea |
|
|
dc.subject.mesh |
Membrane Potential, Mitochondrial |
|
|
dc.subject.mesh |
Cell Line, Tumor |
|
|
dc.subject.mesh |
Structure-Activity Relationship |
|
|
dc.subject.mesh |
Drug Screening Assays, Antitumor |
|
|
dc.subject.mesh |
Molecular Structure |
|
|
dc.subject.mesh |
Cell Proliferation |
|
|
dc.subject.mesh |
Dose-Response Relationship, Drug |
|
|
dc.subject.mesh |
Carbon |
|
|
dc.subject.mesh |
Cell Survival |
|
|
dc.title |
Carbon Chain Length in a Novel Anticancer Aryl-Urea Fatty Acid Modulates Mitochondrial Targeting, Reactive Oxygen Species Production and Cell Killing. |
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|
dc.type |
Journal Article |
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utslib.citation.volume |
19 |
|
|
utslib.location.activity |
Germany |
|
|
utslib.for |
0304 Medicinal and Biomolecular Chemistry |
|
|
utslib.for |
0305 Organic Chemistry |
|
|
utslib.for |
1115 Pharmacology and Pharmaceutical Sciences |
|
|
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/ |
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|
dc.date.updated |
2025-01-30T05:09:34Z |
|
|
pubs.issue |
20 |
|
|
pubs.publication-status |
Published |
|
|
pubs.volume |
19 |
|
|
utslib.citation.issue |
20 |
|
