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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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Citations
Cited by
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Zeng, L., Gupta, P., Chen, Y., Wang, E., Ji, L., Chao, H., & Chen, Z.-S. (2017) · Chemical Society Reviews · doi:10.1039/c7cs00195a · Cited by 1,017
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Hartinger, C. G., & Dyson, P. J. (2009) · Chem. Soc. Rev. · doi:10.1039/b707077m · Cited by 985
Self-citationToward Multi-Targeted Platinum and Ruthenium Drugs—A New Paradigm in Cancer Drug Treatment Regimens?
Kenny, R. G., & Marmion, C. J. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00271 · Cited by 636
Recent developments in ruthenium anticancer drugs
Levina, A., Mitra, A., & Lay, P. A. (2009) · Metallomics · doi:10.1039/b904071d · Cited by 592
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Ang, W. H., Casini, A., Sava, G., & Dyson, P. J. (2011) · Journal of Organometallic Chemistry · doi:10.1016/j.jorganchem.2010.11.009 · Cited by 366
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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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