A potent fluorescent transmembrane HCl transporter perturbs cellular pH and promotes cancer cell death.
Fares, M
Wu, X
McNaughton, DA
Gilchrist, AM
Lewis, W
Keller, PA
Arias-Betancur, A
Fontova, P
Pérez-Tomás, R
Gale, PA
- Publisher:
- Royal Society of Chemistry (RSC)
- Publication Type:
- Journal Article
- Citation:
- Org Biomol Chem, 2023, 21, (12), pp. 2509-2515
- Issue Date:
- 2023-03-22
Closed Access
Filename | Description | Size | |||
---|---|---|---|---|---|
OBC-Final.docx | 11.9 MB | Unknown |
Copyright Clearance Process
- Recently Added
- In Progress
- Closed Access
This item is closed access and not available.
Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Fares, M | |
dc.contributor.author | Wu, X | |
dc.contributor.author | McNaughton, DA | |
dc.contributor.author | Gilchrist, AM | |
dc.contributor.author | Lewis, W | |
dc.contributor.author | Keller, PA | |
dc.contributor.author | Arias-Betancur, A | |
dc.contributor.author | Fontova, P | |
dc.contributor.author | Pérez-Tomás, R | |
dc.contributor.author | Gale, PA | |
dc.date.accessioned | 2023-09-27T04:46:02Z | |
dc.date.available | 2023-09-27T04:46:02Z | |
dc.date.issued | 2023-03-22 | |
dc.identifier.citation | Org Biomol Chem, 2023, 21, (12), pp. 2509-2515 | |
dc.identifier.issn | 1477-0520 | |
dc.identifier.issn | 1477-0539 | |
dc.identifier.uri | http://hdl.handle.net/10453/172324 | |
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 | Electronic | |
dc.language | eng | |
dc.publisher | Royal Society of Chemistry (RSC) | |
dc.relation | http://purl.org/au-research/grants/arc/DP200100453 | |
dc.relation.ispartof | Org Biomol Chem | |
dc.relation.isbasedon | 10.1039/d3ob00128h | |
dc.rights | info:eu-repo/semantics/closedAccess | |
dc.subject | 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry | |
dc.subject.classification | Organic Chemistry | |
dc.subject.classification | 3404 Medicinal and biomolecular chemistry | |
dc.subject.classification | 3405 Organic chemistry | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Adenocarcinoma | |
dc.subject.mesh | Cell Line, Tumor | |
dc.subject.mesh | Colonic Neoplasms | |
dc.subject.mesh | Cell Death | |
dc.subject.mesh | Antineoplastic Agents | |
dc.subject.mesh | Anions | |
dc.subject.mesh | Coumarins | |
dc.subject.mesh | Hydrogen-Ion Concentration | |
dc.subject.mesh | Cell Line, Tumor | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Adenocarcinoma | |
dc.subject.mesh | Colonic Neoplasms | |
dc.subject.mesh | Anions | |
dc.subject.mesh | Coumarins | |
dc.subject.mesh | Antineoplastic Agents | |
dc.subject.mesh | Cell Death | |
dc.subject.mesh | Hydrogen-Ion Concentration | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Adenocarcinoma | |
dc.subject.mesh | Cell Line, Tumor | |
dc.subject.mesh | Colonic Neoplasms | |
dc.subject.mesh | Cell Death | |
dc.subject.mesh | Antineoplastic Agents | |
dc.subject.mesh | Anions | |
dc.subject.mesh | Coumarins | |
dc.subject.mesh | Hydrogen-Ion Concentration | |
dc.title | A potent fluorescent transmembrane HCl transporter perturbs cellular pH and promotes cancer cell death. | |
dc.type | Journal Article | |
utslib.citation.volume | 21 | |
utslib.location.activity | England | |
utslib.for | 0304 Medicinal and Biomolecular Chemistry | |
utslib.for | 0305 Organic Chemistry | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Strength - TKC - The Kidman Centre | |
utslib.copyright.status | closed_access | * |
dc.date.updated | 2023-09-27T04:46:00Z | |
pubs.issue | 12 | |
pubs.publication-status | Published online | |
pubs.volume | 21 | |
utslib.citation.issue | 12 |
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.
Please use this identifier to cite or link to this item:
Download statistics for the last 12 months
Not enough data to produce graph