Novel Antitumor Platinum(II) Conjugates Containing the Nonsteroidal Anti-inflammatory Agent Diclofenac: Synthesis and Dual Mechanisms of Antiproliferative Effects
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F17%3A00476739" target="_blank" >RIV/68081707:_____/17:00476739 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15310/17:73583749
Result on the web
<a href="http://dx.doi.org/10.1021/acs.inorgchem.6b02553" target="_blank" >http://dx.doi.org/10.1021/acs.inorgchem.6b02553</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.inorgchem.6b02553" target="_blank" >10.1021/acs.inorgchem.6b02553</a>
Alternative languages
Result language
angličtina
Original language name
Novel Antitumor Platinum(II) Conjugates Containing the Nonsteroidal Anti-inflammatory Agent Diclofenac: Synthesis and Dual Mechanisms of Antiproliferative Effects
Original language description
One concept how to improve anticancer effects of conventional metallodrugs consists in conjugation of these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, biological effects, and mechanisms of action of new Pt(II) derivatives containing one or two nonsteroidal anti-inflammatory diclofenac (DCF) ligands also known for their antitumor effects. The antiproliferative properties of these metallic conjugates show that these compounds are potent and cancer cell selective cytotoxic agents exhibiting activity in cisplatin resistant and the COX-2 positive tumor cell lines. One of these compounds, compound 3, in which DCF molecules are coordinated to Pt(II) through their carboxylic group, is more potent than parental conventional Pt(II) drug cisplatin, free DCF and the congeners of 3 in which DCF ligands are conjugated to Pt(II) via a diamine. The potency of 3 is due to several factors including enhanced internalization that correlates with enhanced DNA binding and cytotoxicity. Mechanistic studies show that 3 combines multiple effects. After its accumulation in cells, it releases Pt(II) drug capable of binding/damaging DNA and DCF ligands, which affect distribution of cells in individual phases of the cell cycle, inhibit glycolysis and lactate transport, collapse mitochondrial membrane potential, and suppress the cellular properties characteristic of metastatic progression.
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/GA17-05302S" target="_blank" >GA17-05302S: Targeting cancer stem cells by antitumor metallodrugs. Studies on mechanism of action</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Inorganic Chemistry
ISSN
0020-1669
e-ISSN
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Volume of the periodical
56
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
1483-1497
UT code for WoS article
000393630300052
EID of the result in the Scopus database
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