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Anticancer potential of a photoactivated transplatin derivative containing the methylazaindole ligand mediated by ROS generation and DNA cleavage
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SYSNO ASEP 0463802 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Anticancer potential of a photoactivated transplatin derivative containing the methylazaindole ligand mediated by ROS generation and DNA cleavage Author(s) Prachařová, J. (CZ)
Muchová, T. (CZ)
Tomaštíková, Eva (UEB-Q) RID, ORCID
Intini, F. P. (IT)
Pacifico, C. (IT)
Natile, G. (IT)
Kašpárková, Jana (BFU-R) RID, ORCID
Brabec, Viktor (BFU-R) RID, ORCIDSource Title Dalton Transactions. - : Royal Society of Chemistry - ISSN 1477-9226
Roč. 45, č. 33 (2016), s. 13179-13186Number of pages 8 s. Language eng - English Country GB - United Kingdom Keywords PLATINUM-DIIMINE COMPLEX ; SINGLET OXYGEN ; SUPERCOILED DNA Subject RIV CE - Biochemistry R&D Projects GA14-21053S GA ČR - Czech Science Foundation (CSF) LO1204 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support BFU-R - RVO:68081707 ; UEB-Q - RVO:61389030 UT WOS 000382135400025 DOI 10.1039/c6dt01467d Annotation The limitations associated with the clinical utility of conventional platinum anticancer drugs have stimulated research leading to the design of new metallodrugs with improved pharmacological properties, particularly with increased selectivity for cancer cells. Very recent research has demonstrated that photoactivation or photopotentiation of platinum drugs can be one of the promising approaches to tackle this challenge. This is so because the application of irradiation can be targeted exclusively to the tumor tissue so that the resulting effects could be much more selective and targeted to the tumor. We show in this work that the presence of 1-methyl-7-azaindole in trans-[PtCl2(NH3)(L)] (L = 1-methyl-7-azaindole, compound 1) markedly potentiated the DNA binding ability of 1 when irradiated by UVA light in a cell-free medium. Concomitantly, the formation of cytotoxic bifunctional cross-links was markedly enhanced. In addition, 1, when irradiated with UVA, was able to effectively cleave the DNA backbone also in living cells. The incorporation of 1-methyl-7-azaindole moiety had also a profound effect on the photophysical properties of 1, which can generate singlet oxygen responsible for the DNA cleavage reaction. Finally, we found that 1, upon irradiation with UVA light, exhibited a pronounced dose-dependent decrease in viability of A2780 cells whereas it was markedly less cytotoxic if the cells were treated in the absence of light. Hence, it is possible to conclude that 1 is amenable to photodynamic therapy. Workplace Institute of Experimental Botany Contact David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Year of Publishing 2017
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