Antitumor substitution-inert polynuclear platinum complexes stabilize G-quadruplex DNA and suppress G-quadruplex-mediated gene expression
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F21%3A00554901" target="_blank" >RIV/68081707:_____/21:00554901 - isvavai.cz</a>
Result on the web
<a href="https://pubs.rsc.org/en/content/articlelanding/2021/QI/D1QI00488C" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2021/QI/D1QI00488C</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/d1qi00488c" target="_blank" >10.1039/d1qi00488c</a>
Alternative languages
Result language
angličtina
Original language name
Antitumor substitution-inert polynuclear platinum complexes stabilize G-quadruplex DNA and suppress G-quadruplex-mediated gene expression
Original language description
DNA G-quadruplex (G4) structures formed in the telomeric and promoter regions represent attractive drug targets for anticancer therapy. Thus, much effort has been devoted to the development of a variety of G4-binding ligands, mostly based on rigid planar structures. Here, we investigated the efficacy of inherently flexible anticancer substitution-inert polynuclear platinum(s) complexes (SI-PPCs) to stabilize DNA G4s and terminate DNA polymerization on templates containing G4-forming sequences. Conventional DNA polymerase primer extension assay, fluorescence melting studies, fluorescence indicator displacement assay and circular dichroism spectroscopy revealed that SI-PPCs can stabilize DNA G4s and terminate DNA polymerization on templates containing G4-forming sequences although they lack structural properties of traditional G4 binders. Despite that the selectivity for G4 DNA over double-stranded DNA was somewhat lower than that observed for some traditional G4-binding ligands, it was notable that one of the investigated SI-PPCs, anticancer Triplatin NC, reduced the expression of G4-regulated genes c-myc and c-kit in human embryonic kidney cells. These results demonstrate that the overall biological activity of SI-PPCs can also involve interactions of SI-PPCs with different cellular targets acting as multi-target-directed compounds.
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
10401 - Organic chemistry
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
2021
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 Frontiers
ISSN
2052-1553
e-ISSN
2052-1553
Volume of the periodical
8
Issue of the periodical within the volume
13
Country of publishing house
GB - UNITED KINGDOM
Number of pages
11
Pages from-to
3371-3381
UT code for WoS article
000660065800001
EID of the result in the Scopus database
2-s2.0-85109094177