Molecular superoxide radical photogeneration in cancer cells by dipyridophenazine iridium(III) complexes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F19%3A00518329" target="_blank" >RIV/68081707:_____/19:00518329 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/19:73597258

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlelanding/2019/QI/C9QI00811J#!divAbstract" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2019/QI/C9QI00811J#!divAbstract</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c9qi00811j" target="_blank" >10.1039/c9qi00811j</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Molecular superoxide radical photogeneration in cancer cells by dipyridophenazine iridium(III) complexes

Popis výsledku v původním jazyce

The phototoxicity in cancer cells of three series of octahedral Ir(III) complexes of the general formula [Ir(C<^>N)(2)(N<^>N)][PF6], where the N<^>N ligand is dipyrido[3,2-a:2',3'-c]phenazine (dppz) and the C<^>N ligands are deprotonated 2-phenyl-, 2-(naphthalen-2-yl)-or 2-(thiophen-2-yl)-benzimidazole derivatives (series 1, 2 and 3, respectively) with different substituents (H, methyl or 4-(trifluoromethyl)benzyl) on the imidazole units, has been studied. The 1-methyl benzimidazole compounds 2b and 3b were found to be the most photoactive in model human cervical cancer HeLa cells (IC50 about 20 nM under irradiation conditions, lambda(exc) = 420 nm), inducing a substantial formation of apoptotic bodies as shown by flow cytometry, whereas the 4-(trifluoromethyl)benzyl derivatives 1c-3c showed the highest phototoxic indexes of the three series. Notably, the antiproliferative activity of the photoactivated Ir(III) compounds was also significant under hypoxic conditions (2% O-2). Fluorescence confocal microscopy investigation for 1c, 2c and 3c was undertaken, showing a significant subcellular localization of 3c in mitochondria, whereas 1c and 2c were located preferentially in the endoplasmic reticulum (ER). Further investigations on series 3 compounds using CellRox (R) (oxidative stress deep red reagent) have shown, after pretreatment with Tiron, that molecular superoxide radical (O-2(center dot-)) generation is mainly responsible for the oxidative stress induced by irradiation of the cells treated with the 2-(thiophen-2-yl)benzimidazole derivatives 3a-c. The photopotentiation of 3a and 3c also involves the formation of singlet oxygen (O-1(2)), but this does not occur with 3b, due to pretreatment with sodium azide. The ROS generation was also studied by standard droethidium (DHE) and singlet oxygen sensor green (SOSG) staining assays under both normoxic and hypoxic conditions. The results showed that in tumor HeLa cells, the generation of superoxide radicals competed with singlet oxygen production in cells in normoxia, but became dominant under hypoxia.

Název v anglickém jazyce

Molecular superoxide radical photogeneration in cancer cells by dipyridophenazine iridium(III) complexes

Popis výsledku anglicky

The phototoxicity in cancer cells of three series of octahedral Ir(III) complexes of the general formula [Ir(C<^>N)(2)(N<^>N)][PF6], where the N<^>N ligand is dipyrido[3,2-a:2',3'-c]phenazine (dppz) and the C<^>N ligands are deprotonated 2-phenyl-, 2-(naphthalen-2-yl)-or 2-(thiophen-2-yl)-benzimidazole derivatives (series 1, 2 and 3, respectively) with different substituents (H, methyl or 4-(trifluoromethyl)benzyl) on the imidazole units, has been studied. The 1-methyl benzimidazole compounds 2b and 3b were found to be the most photoactive in model human cervical cancer HeLa cells (IC50 about 20 nM under irradiation conditions, lambda(exc) = 420 nm), inducing a substantial formation of apoptotic bodies as shown by flow cytometry, whereas the 4-(trifluoromethyl)benzyl derivatives 1c-3c showed the highest phototoxic indexes of the three series. Notably, the antiproliferative activity of the photoactivated Ir(III) compounds was also significant under hypoxic conditions (2% O-2). Fluorescence confocal microscopy investigation for 1c, 2c and 3c was undertaken, showing a significant subcellular localization of 3c in mitochondria, whereas 1c and 2c were located preferentially in the endoplasmic reticulum (ER). Further investigations on series 3 compounds using CellRox (R) (oxidative stress deep red reagent) have shown, after pretreatment with Tiron, that molecular superoxide radical (O-2(center dot-)) generation is mainly responsible for the oxidative stress induced by irradiation of the cells treated with the 2-(thiophen-2-yl)benzimidazole derivatives 3a-c. The photopotentiation of 3a and 3c also involves the formation of singlet oxygen (O-1(2)), but this does not occur with 3b, due to pretreatment with sodium azide. The ROS generation was also studied by standard droethidium (DHE) and singlet oxygen sensor green (SOSG) staining assays under both normoxic and hypoxic conditions. The results showed that in tumor HeLa cells, the generation of superoxide radicals competed with singlet oxygen production in cells in normoxia, but became dominant under hypoxia.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Inorganic Chemistry Frontiers

ISSN

2052-1553

e-ISSN

—

Svazek periodika

6

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

2500-2513

Kód UT WoS článku

000491293500031

EID výsledku v databázi Scopus

—