- Title
- Warburg effect targeting Co(III) cytotoxin chaperone complexes
- Creator
- Glenister, Alexandra; Chen, Catherine K. J.; Paterson, David J.; Renfrew, Anna K.; Simone, Michela I.; Hambley, Trevor W.
- Relation
- Journal of Medicinal Chemistry Vol. 64, Issue 5, p. 2678-2690
- Publisher Link
- http://dx.doi.org/10.1021/acs.jmedchem.0c01875
- Publisher
- American Chemical Society
- Resource Type
- journal article
- Date
- 2021
- Description
- A glucose-based vector for targeting cancer cells conjugated to a tris(methylpyridyl)amine (tpa) ligand to generate targeted chaperone and caging complexes for active anticancer agents is described. The ligand, tpa(CONHPEGglucose)1, inhibits hexokinase, suggesting that it will be phosphorylated in the cell. A Co(III) complex incorporating this ligand and coumarin-343 hydroximate (C343ha), [Co(C343ha){tpa(CONHPEGglucose)1}]Cl, is shown to exhibit glucose-dependent cellular accumulation in DLD-1 colon cancer cells. Cellular accumulation of [Co(C343ha){tpa(CONHPEGglucose)1}]+ is slower than for the glucose null and glucosamine analogues, and the glucose complex also exhibits a lower ability to inhibit antiproliferative activity. Distributions of cobalt (X-ray fluorescence) and C343ha (visible light fluorescence) in DLD-1 cancer cell spheroids are consistent with uptake of [Co(C343ha){tpa(CONHPEGglucose)1}]+ by rapidly dividing cells, followed by release and efflux of C343ha and trapping of the Co{tpa(CONHPEGglucose)1} moiety. The Co{tpa(CONHPEGglucose)1} moiety is shown to have potential for the caged and targeted delivery of highly toxic anticancer agents.
- Subject
- glucose-based; cancer cells; cancer cell spheroids; toxic anticancer agents; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1461855
- Identifier
- uon:46316
- Identifier
- ISSN:1520-4804
- Language
- eng
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