Dicobalt(II) helices kill colon cancer cells <i>via</i> enantiomer-specific mechanisms, DNA damage or microtubule disruption
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Dicobalt(II) helices kill colon cancer cells <i>via</i> enantiomer-specific mechanisms, DNA damage or microtubule disruption
Original language description
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.
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
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Chemical Science
ISSN
2041-6520
e-ISSN
2041-6539
Volume of the periodical
15
Issue of the periodical within the volume
28
Country of publishing house
GB - UNITED KINGDOM
Number of pages
9
Pages from-to
11029-11037
UT code for WoS article
001251036000001
EID of the result in the Scopus database
2-s2.0-85196488173