N-Indolyl diiron vinyliminium complexes exhibit antiproliferative effects in cancer cells associated with disruption of mitochondrial homeostasis, ROS scavenging, and antioxidant activity
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F23%3A00583469" target="_blank" >RIV/68081707:_____/23:00583469 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/23:00132046 RIV/61989592:15310/23:73620577
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S000927972300409X?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S000927972300409X?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.cbi.2023.110742" target="_blank" >10.1016/j.cbi.2023.110742</a>
Alternative languages
Result language
angličtina
Original language name
N-Indolyl diiron vinyliminium complexes exhibit antiproliferative effects in cancer cells associated with disruption of mitochondrial homeostasis, ROS scavenging, and antioxidant activity
Original language description
The indole scaffold has been established as a key organic moiety for developing new drugs, on the other hand, a range of diiron bis-cyclopentadienyl complexes have recently emerged for their promising anticancer potential. Here, we report the synthesis of novel diiron complexes with an indole-functionalized vinyliminium ligand (2-5) and an indole-lacking analogue for comparative purposes (6), which were characterized by analytical and spectroscopic techniques. Complexes 2-6 are substantially stable in DMSO-d6 and DMEM-d solutions at 37 degrees C (8% average degradation after 48 h) and display a balanced hydrophilic/lipophilic behaviour (LogPow values in the range0.32 to 0.47), associated with appreciable water solubility. The complexes display selective antiproliferative potency towards several cancer cells in monolayer cultures, mainly in the low micromolar range, with reduced toxicity towards noncancerous epithelial cells. Thus, the cytotoxicity of the complexes is comparable to or better than clinically used metallopharmaceutical cisplatin. Comparing the antiproliferative activity obtained for complexes containing different ligands, we confirmed the importance of the indolyl group in the mechanism of antiproliferative activity of these complexes. Cell-based mechanistic studies suggest that the investigated diiron vinyliminium complexes (DVCs) show cytostatic rather than cytotoxic effects and subsequently induce a population of cells to undergo apoptosis. Furthermore, the molecular mechanism of action involves interactions with mitochondrial DNA and proteins, the reactive oxygen species (ROS)-scavenging properties and antioxidant activity of these complexes in cancer cells. This study highlights the importance of DVCs to their cancer cell activity and reinforces their prospective therapeutic potential as anticancer agents.
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
<a href="/en/project/GA23-06316S" target="_blank" >GA23-06316S: Medicinal biophysics and biochemistry of light-activated metallodrugs for targeted cancer therapy.</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Chemico-Biological Interactions
ISSN
0009-2797
e-ISSN
1872-7786
Volume of the periodical
385
Issue of the periodical within the volume
NOV 1 2023
Country of publishing house
IE - IRELAND
Number of pages
15
Pages from-to
110742
UT code for WoS article
001094243700001
EID of the result in the Scopus database
2-s2.0-85173242183