Dicobalt(II) helices kill colon cancer cells <i>via</i> enantiomer-specific mechanisms, DNA damage or microtubule disruption

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F24%3A00587843" target="_blank" >RIV/68081707:_____/24:00587843 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlelanding/2024/sc/d4sc02541e" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2024/sc/d4sc02541e</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d4sc02541e" target="_blank" >10.1039/d4sc02541e</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Dicobalt(II) helices kill colon cancer cells <i>via</i> enantiomer-specific mechanisms, DNA damage or microtubule disruption

Popis výsledku v původním jazyce

Highly diastereoselective self-assembly reactions give both enantiomers (Lambda and Delta) of anti-parallel triple-stranded bimetallic Co(ii) and Co(iii) cationic helices, without the need for resolution, the first such reaction for Co. The complexes are water soluble and stable, even in the case of Co(ii). Studies in a range of cancer and healthy cell lines indicate high activity and selectivity, and substantial differences between enantiomers. The oxidation state has little effect, and correspondingly, Co(iii) compounds are reduced to Co(ii) e.g. by glutathione. In HCT116 colon cancer cells the Lambda enantiomer induces dose-dependent G2-M arrest in the cell cycle and disrupts microtubule architectures. This Co(ii) Lambda enantiomer is ca. five times more potent than the isostructural Fe(ii) compound. Since the measured cellular uptakes are similar this implies a higher affinity of the Co system for the intracellular target(s), while the two systems are isostructural they have substantially different charge distributions as shown by calculated hydrophobicity maps. In contrast to the Lambda enantiomer, Delta-Co(ii) induces G1 arrest in HCT116 cells, efficiently inhibits the topoisomerase I-catalyzed relaxation of supercoiled plasmid DNA, and, unlike the isostructural Fe(ii) system, causes DNA damage. It thus seems very likely that redox chemistry plays a role in the latter.

Název v anglickém jazyce

Dicobalt(II) helices kill colon cancer cells <i>via</i> enantiomer-specific mechanisms, DNA damage or microtubule disruption

Popis výsledku anglicky

Highly diastereoselective self-assembly reactions give both enantiomers (Lambda and Delta) of anti-parallel triple-stranded bimetallic Co(ii) and Co(iii) cationic helices, without the need for resolution, the first such reaction for Co. The complexes are water soluble and stable, even in the case of Co(ii). Studies in a range of cancer and healthy cell lines indicate high activity and selectivity, and substantial differences between enantiomers. The oxidation state has little effect, and correspondingly, Co(iii) compounds are reduced to Co(ii) e.g. by glutathione. In HCT116 colon cancer cells the Lambda enantiomer induces dose-dependent G2-M arrest in the cell cycle and disrupts microtubule architectures. This Co(ii) Lambda enantiomer is ca. five times more potent than the isostructural Fe(ii) compound. Since the measured cellular uptakes are similar this implies a higher affinity of the Co system for the intracellular target(s), while the two systems are isostructural they have substantially different charge distributions as shown by calculated hydrophobicity maps. In contrast to the Lambda enantiomer, Delta-Co(ii) induces G1 arrest in HCT116 cells, efficiently inhibits the topoisomerase I-catalyzed relaxation of supercoiled plasmid DNA, and, unlike the isostructural Fe(ii) system, causes DNA damage. It thus seems very likely that redox chemistry plays a role in the latter.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Chemical Science

ISSN

2041-6520

e-ISSN

2041-6539

Svazek periodika

15

Číslo periodika v rámci svazku

28

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

11029-11037

Kód UT WoS článku

001251036000001

EID výsledku v databázi Scopus

2-s2.0-85196488173