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

Result code in 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>

Alternative codes found

RIV/61989592:15310/19:73597258

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10402 - Inorganic and nuclear chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2019

Confidentiality

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

Name of the periodical

Inorganic Chemistry Frontiers

ISSN

2052-1553

e-ISSN

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Volume of the periodical

6

Issue of the periodical within the volume

9

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

2500-2513

UT code for WoS article

000491293500031

EID of the result in the Scopus database

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