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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

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • 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