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 | |
| 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
|
cienciaabierta.ufro.cl
ciencia.abierta@ufrontera.cl