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http://hdl.handle.net/2445/208114
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DC Field | Value | Language |
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dc.contributor.author | Gale, Philip A. | - |
dc.contributor.author | Fares, Mohamed | - |
dc.contributor.author | Wu, Xin | - |
dc.contributor.author | McNaughton, Daniel A. | - |
dc.contributor.author | Gilchrist, Alexander M. | - |
dc.contributor.author | Lewis, William | - |
dc.contributor.author | Keller, Paul A. | - |
dc.contributor.author | Arias-Betancur, Alain | - |
dc.contributor.author | Fontova, Pere | - |
dc.contributor.author | Pérez-Tomás, Ricardo | - |
dc.date.accessioned | 2024-02-27T14:10:07Z | - |
dc.date.available | 2024-03-06T06:10:16Z | - |
dc.date.issued | 2023-03-07 | - |
dc.identifier.issn | 1477-0520 | - |
dc.identifier.uri | http://hdl.handle.net/2445/208114 | - |
dc.description.abstract | A series of fluorescent coumarin bis-ureas 1-4 have been synthesised, and their anion transport properties studied. The compounds function as highly potent HCl co-transport agents in lipid bilayer membranes. Single crystal X-ray diffraction of compound 1 showed antiparallel stacking of the coumarin rings, stabilised by hydrogen bonds. Binding studies, using 1H-NMR titration, showed moderate chloride binding in DMSO-d6/0.5% with 1 : 1 binding mode (for transporter 1) and 1 : 2 binding mode (host: guest, for transporters 2-4). We examined the cytotoxicity of compounds 1-4 against three cancer cell lines, lung adenocarcinoma (A549), colon adenocarcinoma (SW620) and breast adenocarcinoma (MCF-7). The most lipophilic transporter, 4 showed a cytotoxic effect against all three cancer cell lines. Cellular fluorescence studies showed compound 4 crossed the plasma membrane and localised in the cytoplasm after a short time. Interestingly, compound 4, lacking any lysosome targeting groups, was co-localised with LysoTracker Red at 4 and 8 h in the lysosome. Cellular anion transport of compound 4 was assessed by measuring intracellular pH and showed a decrease in cellular pH, which may be due to the capacity of transporter 4 to co-transport HCl across biological membranes, as evidenced by the liposomal studies. | - |
dc.format.extent | 7 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Royal Society of Chemistry | - |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1039/d3ob00128h | - |
dc.relation.ispartof | Organic & Biomolecular Chemistry, 2023, vol. 21, num.12, p. 2509-2515 | - |
dc.relation.uri | https://doi.org/10.1039/d3ob00128h | - |
dc.rights | (c) Fares, M. et al., 2023 | - |
dc.source | Articles publicats en revistes (Patologia i Terapèutica Experimental) | - |
dc.subject.classification | Càncer | - |
dc.subject.classification | Anions | - |
dc.subject.classification | Mort cel·lular | - |
dc.subject.classification | Medicaments antineoplàstics | - |
dc.subject.other | Cancer | - |
dc.subject.other | Anions | - |
dc.subject.other | Cell death | - |
dc.subject.other | Antineoplastic agents | - |
dc.title | A potent fluorescent transmembrane HCl transporter perturbs cellular pH and promotes cancer cell death | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 743691 | - |
dc.date.updated | 2024-02-27T14:10:07Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 36880402 | - |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) |
Files in This Item:
File | Description | Size | Format | |
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845404.pdf | 822.99 kB | Adobe PDF | View/Open |
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