Repositorio UFRO · Omeka S

A potent fluorescent transmembrane HCl transporter perturbs cellular pH and promotes cancer cell death

Primer Autor	Gale, Philip A.
Co-autores	Fares, Mohamed Wu, Xin McNaughton, Daniel A. Gilchrist, Alexander M. Lewis, William Keller, Paul A. Arias-Betancur, Alain Fontova, Pere Perez-Tomas, Ricardo
Título	A potent fluorescent transmembrane HCl transporter perturbs cellular pH and promotes cancer cell death
Editorial	ROYAL SOC CHEMISTRY
Revista	ORGANIC & BIOMOLECULAR CHEMISTRY
Lenguaje	en
Resumen	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 H-1-NMR titration, showed moderate chloride binding in DMSO-d(6)/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.
Fecha Publicación	2023
Tipo de Recurso	artículo original
doi	10.1039/d3ob00128h
Formato Recurso	PDF
Palabras Claves	Adenocarcinoma Anions / chemistry Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology Cell Death Cell Line, Tumor Colonic Neoplasms Coumarins / pharmacology Humans Hydrogen-Ion Concentration
Ubicación del archivo	http://dx.doi.org/10.1039/d3ob00128h
Categoría OCDE	Química
Materias	Adenocarcinoma Aniones/química Agentes Antineoplásicos / Química Agentes Antineoplásicos / Farmacología Muerte Celular Línea Celular, Tumor Neoplasias del Colon Cumarinas/farmacología Humanos iones de hidrógeno Concentración
Página de inicio (Recomendado-único)	2509.0
Página final (Recomendado-único)	2515
Identificador del recurso (Mandatado-único)	artículo original
Versión del recurso (Recomendado-único)	versión publicada
Derechos de acceso	metadata
Identificador relacionado	https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/615e344cf718df61bbd60b70/original/coumarin-bisureas-as-potent-fluorescent-transmembrane-anion-transporters.pdf
Access Rights	metadata
Id de Web of Science	WOS:000944248400001
ISSN	1477-0520
Tipo de ruta	verde
Categoría WOS	Química
Referencia del Financiador (Mandatado si es aplicable-repetible)	ARC DP200100453