Novel cis-Pt(II) Complexes with Alkylpyrazole Ligands: Synthesis, Characterization, and Unusual Mode of Anticancer Action
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F22%3A00556796" target="_blank" >RIV/68081707:_____/22:00556796 - isvavai.cz</a>
Result on the web
<a href="https://www.hindawi.com/journals/bca/2022/1717200/" target="_blank" >https://www.hindawi.com/journals/bca/2022/1717200/</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1155/2022/1717200" target="_blank" >10.1155/2022/1717200</a>
Alternative languages
Result language
angličtina
Original language name
Novel cis-Pt(II) Complexes with Alkylpyrazole Ligands: Synthesis, Characterization, and Unusual Mode of Anticancer Action
Original language description
One concept of improving anticancer effects of conventional platinum-based antitumor drugs consists of conjugating these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, physicochemical characterization, biological effects, and mechanisms of action of four new analogs of conventional cisplatin, namely, cis-Pt(II) complexes containing either methyl or ethyl pyrazole N-donor ligands and chlorido or iodido ligands. It is noteworthy that while chlorido complexes display activity in a variety of cancer cell lines comparable to cisplatin, iodido complexes are considerably more potent due to their enhanced hydrophobicity and consequently enhanced cellular accumulation. Moreover, all of the studied Pt(II) alkylpyrazole complexes display a higher selectivity for tumor cells and effectively overcome the acquired resistance to cisplatin. Further results focused on the mechanism of action of the studied complexes and showed that in contrast to cisplatin and several platinum-based antitumor drugs, DNA damage by the investigated Pt(II)-alkylpyrazole complexes does not play a major role in their mechanism of action. Our findings demonstrate that inhibition of the tubulin kinesin Eg5, which is essential for forming a functional mitotic spindle, plays an important role in their mechanism of antiproliferative action.
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
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GC20-14082J" target="_blank" >GC20-14082J: Development of new, targeting polynuclear platinum and ruthenium complexes for anticancer chemotherapy. Mechanism of action</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Bioinorganic Chemistry and Applications
ISSN
1565-3633
e-ISSN
1687-479X
Volume of the periodical
2022
Issue of the periodical within the volume
MAR 2 2022
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
1717200
UT code for WoS article
000778347200002
EID of the result in the Scopus database
2-s2.0-85126335325