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• W3118144831 startingPage "127750" @default.
• W3118144831 abstract "Targeting specific mitochondrial alterations to kill cancer cells without affecting their normal counterparts emerges as a feasible strategy. Coumarin derivatives have demonstrated the potential anti-breast cancer activities. By coupling coumarin-3-carboxamide derivatives with mitochondria carrier triphenylphosphonium, mitocoumarins 15a-c were produced and tested as the anti-breast cancer fluorescence agents. Among them, 15b as the amide-based drug potently suppressed the cell growth in MCF-7, MDA-231, SK-BR-3 breast cancer cells with the IC50 values from 3.0 to 4.1 μM, including the lower cytotoxicity to normal MCF-10A cells with the IC50 value around 45.30 ± 2.45 μM. In mechanistic study for 15b in MDA-MB-231 cells, it could localize in mitochondria to elicit ROS burst and collapse Δψm. Besides, it could deplete GSH by an irreversible alkylation process and moderately inhibit mitochondrial thioredoxin reductase TrxR2, thus leading to aggravate cellular oxidative stress. This study reported 15b might be useful for the further development into a mitochondria-targeted anti-triple negative breast cancer drug." @default.
• W3118144831 created "2021-01-05" @default.
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• W3118144831 date "2021-02-01" @default.
• W3118144831 modified "2023-10-16" @default.
• W3118144831 title "Synthesis of mitochondria-targeted coumarin-3-carboxamide fluorescent derivatives: Inhibiting mitochondrial TrxR2 and cell proliferation on breast cancer cells" @default.
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• W3118144831 doi "https://doi.org/10.1016/j.bmcl.2020.127750" @default.
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