Antitumoral effects of mitochondria-targeting neutral and cationic cis-[bis(1,3-dibenzylimidazol-2-ylidene)Cl(L)]Pt(II) complexes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F20%3A00535789" target="_blank" >RIV/68081707:_____/20:00535789 - isvavai.cz</a>
Result on the web
<a href="https://pubs.rsc.org/en/content/articlelanding/2020/DT/D0DT01664K#!divAbstract" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2020/DT/D0DT01664K#!divAbstract</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/d0dt01664k" target="_blank" >10.1039/d0dt01664k</a>
Alternative languages
Result language
angličtina
Original language name
Antitumoral effects of mitochondria-targeting neutral and cationic cis-[bis(1,3-dibenzylimidazol-2-ylidene)Cl(L)]Pt(II) complexes
Original language description
Recently, we opened a synthetic access to antitumoral platinum complexes of the typecis-[(NHC)(1)(NHC)(PtCl)-Pt-2-Cl-II(L)] which interact with DNA in a way correlated to the complex charge and to the sterical accessibility of the leaving chlorido ligand. We now identified mitochondria rather than nuclei as the cellular target of the neutral dichlorido complex1(L = Cl) and the delocalized lipophilic cationic phosphine complex2(L = PPh3), both carrying the samecis-bis(1,3-dibenzylimidazol-2-ylidene) ligands. Their uptake into 518A2 melanoma cells was concentration-dependent and distinctly greater for complex2which was also more cytotoxic against sensitive cancer cell lines with submicromolar IC(50)values. Both complexes interfered strongly with various forms of DNAin vitro, but only complex2caused a melanoma cell cycle arrest in G1-phase, setting both apart from the S-phase arresting drug cisplatin. Studies of the intracellular localisation of1and2were carried out with their alkyne-tagged analogues6and7, which showed identical patterns of cancer cell cytotoxicity, cell cycle interference and effects on mitochondria. Click reactions with 7-hydroxycoumarin azide, colocalisation with Mitotracker (TM) and confocal microscopy, proved complexes6and7to accumulate mainly in the mitochondria rather than the nuclei of melanoma cells. Complex1and even more so complex2reduced the mitochondrial membrane potential and also increased the cellular ROS levels. As a consequence, both complexes caused stress fibre formation in the F-actin cytoskeleton of melanoma cells, most distinctly so complex2which also activated the apoptotic cascade mediated by capases-3 and7.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - 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
Result continuities
Project
<a href="/en/project/GA18-09502S" target="_blank" >GA18-09502S: Targeting resistance to chemotherapy of tumor cells to reinstate their susceptibility to novel, existing and unsuccessful anticancer metallodrugs</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Dalton Transactions
ISSN
1477-9226
e-ISSN
—
Volume of the periodical
49
Issue of the periodical within the volume
26
Country of publishing house
GB - UNITED KINGDOM
Number of pages
10
Pages from-to
8901-8910
UT code for WoS article
000552458700009
EID of the result in the Scopus database
2-s2.0-85087768365