Platinum(II) Iodido Complexes of 7-Azaindoles with Significant Antiproliferative Effects: An Old Story Revisited with Unexpected Outcomes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F16%3A33161196" target="_blank" >RIV/61989592:15310/16:33161196 - isvavai.cz</a>
Result on the web
<a href="http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0165062&type=printable" target="_blank" >http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0165062&type=printable</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1371/journal.pone.0165062" target="_blank" >10.1371/journal.pone.0165062</a>
Alternative languages
Result language
angličtina
Original language name
Platinum(II) Iodido Complexes of 7-Azaindoles with Significant Antiproliferative Effects: An Old Story Revisited with Unexpected Outcomes
Original language description
A series of platinum(II) diiodido complexes containing 7-azaindole derivatives, having the general formula cis-[ PtI2(naza)(2)] (1-8), has been prepared and thoroughly characterized, including X-ray structure analysis of cis-[ PtI2(2Me4Claza)(2)].DMF (8.DMF; 2Me4Claza = 2-methyl-4-chloro-7-azaindole). Complexes showed high in vitro cytotoxicity against nine human cancer cell lines (IC50 ranging from 0.4 to 12.8 mu M), including the cisplatin-resistant ovarian cancer cell line (A2780R; IC50 = 1.0-3.5 mu M). The results of in vivo testing, using the L1210 lymphocytic leukaemia model, at the equimolar doses of Pt with cisplatin (2 mg/kg) confirmed the activity of complex 8 comparable to cisplatin. From the mechanistic point of view, evaluated ex vivo by Western blot analyses on the samples of isolated tumour tissues, the treatment of the animals with complex 8, contrary to cisplatin, decreased the levels of tumour suppressor p53 and increased significantly the amount of intracellular anti-apoptotic protein MCL-1(L) (37 kDa). Additionally, the active form of caspase 3 was significantly elevated in the sample of tumour tissues treated with complex 8, indicating that the activation of p53-independent cell-death pathway was initiated. The light and electron microscopy observations of the cancerous tissues revealed necrosis as a dominant mechanism of cell death, followed by scarce signs of apoptosis. The additional results (e.g. in vitro interaction experiments with selected biomolecules, cell cycle perturbations, gel electrophoretic studies on pUC19 plasmid DNA) supported the hypothesis that the complexes might be involved in the mechanism of action quite different from cisplatin.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CA - Inorganic chemistry
OECD FORD branch
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Result continuities
Project
<a href="/en/project/LO1305" target="_blank" >LO1305: Development of the center of advanced technologies and materials</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
PLoS One
ISSN
1932-6203
e-ISSN
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Volume of the periodical
11
Issue of the periodical within the volume
12
Country of publishing house
US - UNITED STATES
Number of pages
25
Pages from-to
"e0165062-1"-"e0165062-25"
UT code for WoS article
000389482700007
EID of the result in the Scopus database
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