Carbon Chain Length in a Novel Anticancer Aryl-Urea Fatty Acid Modulates Mitochondrial Targeting, Reactive Oxygen Species Production and Cell Killing.
ChemMedChem
; : e202400281, 2024 Jun 30.
Article
em En
| MEDLINE
| ID: mdl-38945837
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±0.8â
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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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Austrália