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Development of Ruthenium Antitumor Drugs that Overcome Multidrug Resistance Mechanisms
Open accessAbstract
Organometallic ruthenium(II) complexes of the general formula [Ru(eta6-p-cymene)Cl2(L)] and [Ru(eta6-p-cymene)Cl(L)2][BPh4] with modified phenoxazine- and anthracene-based multidrug resistance (MDR) modulator ligands (L) have been synthesized, spectroscopically characterized, and evaluated in vitro for their cytotoxic and MDR reverting properties in comparison with the free ligands. For an anthracene-based ligand, coordination to a ruthenium(II) arene fragment led to significant improvement of cytotoxicity as well as Pgp inhibition activity. A similar, but weaker effect was also observed when using a benzimidazole-phenoxazine derivative as Pgp inhibitor. The most active compound in terms of both Pgp inhibition and cytotoxicity is [Ru(eta6-p-cymene)Cl2(L)], where L is an anthracene-based ligand. Studies show that it induces cell death via inhibition of DNA synthesis. Moreover, because the complex is fluorescent, its uptake in cells was studied, and relative to the free anthracene-based ligand, uptake of the complex is accelerated and accumulation of the complex in the cell nucleus is observed.
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Cited by
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Hartinger, C. G., & Dyson, P. J. (2009) · Chem. Soc. Rev. · doi:10.1039/b707077m · Cited by 985
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Metadata
- Authors
- Vock, C. A., Ang, W. H., Scolaro, C., Phillips, A. D., Lagopoulos, L., Juillerat-Jeanneret, L., Sava, G., Scopelliti, R., & Dyson, P. J.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2007-04-10
- Volume
- 50
- Issue
- 9
- Pages
- 2166-2175
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W1981603699
- Cited by
- 185
- References
- 0
- FWCI
- 8.00
- Type
- journal article
- Language
- en
- Open access
- green
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- Vock, C. A., Ang, W. H., Scolaro, C., Phillips, A. D., Lagopoulos, L., Juillerat-Jeanneret, L., Sava, G., Scopelliti, R., & Dyson, P. J. (2007). Development of Ruthenium Antitumor Drugs that Overcome Multidrug Resistance Mechanisms. Journal of Medicinal Chemistry. https://doi.org/10.1021/jm070039f
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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