Antitumor substitution-inert polynuclear platinum complexes stabilize G-quadruplex DNA and suppress G-quadruplex-mediated gene expression

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Antitumor substitution-inert polynuclear platinum complexes stabilize G-quadruplex DNA and suppress G-quadruplex-mediated gene expression

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Antitumor substitution-inert polynuclear platinum complexes stabilize G-quadruplex DNA and suppress G-quadruplex-mediated gene expression

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GC20-14082J" target="_blank" >GC20-14082J: Vývoj nových, cílených vícejaderných komplexů platiny a ruthenia pro chemoterapii rakoviny. Mechanimus působení</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Inorganic Chemistry Frontiers

ISSN

2052-1553

e-ISSN

2052-1553

Svazek periodika

8

Číslo periodika v rámci svazku

13

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

3371-3381

Kód UT WoS článku

000660065800001

EID výsledku v databázi Scopus

2-s2.0-85109094177