Anticancer potential of a photoactivated transplatin derivative containing the methylazaindole ligand mediated by ROS generation and DNA cleavage
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F16%3A00463802" target="_blank" >RIV/68081707:_____/16:00463802 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/61389030:_____/16:00463802 RIV/61989592:15310/16:33161170
Výsledek na webu
<a href="http://dx.doi.org/10.1039/c6dt01467d" target="_blank" >http://dx.doi.org/10.1039/c6dt01467d</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/c6dt01467d" target="_blank" >10.1039/c6dt01467d</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Anticancer potential of a photoactivated transplatin derivative containing the methylazaindole ligand mediated by ROS generation and DNA cleavage
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
Anticancer potential of a photoactivated transplatin derivative containing the methylazaindole ligand mediated by ROS generation and DNA cleavage
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>x</sub> - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)
CEP obor
CE - Biochemie
OECD FORD obor
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Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2016
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Dalton Transactions
ISSN
1477-9226
e-ISSN
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Svazek periodika
45
Číslo periodika v rámci svazku
33
Stát vydavatele periodika
GB - Spojené království Velké Británie a Severního Irska
Počet stran výsledku
8
Strana od-do
13179-13186
Kód UT WoS článku
000382135400025
EID výsledku v databázi Scopus
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