Highly effective Ru(II) and Os(II) half-sandwich complexes induce cytotoxicity in cancer cells through combined mitochondrial and endoplasmic reticulum stress
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F25%3AN0000064" target="_blank" >RIV/00027162:_____/25:N0000064 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15310/25:73633985
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0223523425007354" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0223523425007354</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmech.2025.117970" target="_blank" >10.1016/j.ejmech.2025.117970</a>
Alternative languages
Result language
angličtina
Original language name
Highly effective Ru(II) and Os(II) half-sandwich complexes induce cytotoxicity in cancer cells through combined mitochondrial and endoplasmic reticulum stress
Original language description
A series of ruthenium(II) and osmium(II) half-sandwich complexes was synthesized and characterized for its potential as a new class of anticancer agents. The complexes feature polycyclic aromatic hydrocarbon (PAH)- substituted Schiff bases and were rationally designed to combine the redox-modulating MoA of half-sandwich Ru, Rh, Os and Ir complexes, connected with their ability to induce the formation of various reactive oxygen species (ROS), with the ability of PAH-substituents to target and disrupt DNA. The complexes [Ru(η6-pcym)Cl(L)] PF6 (1–4) and [Os(η6-pcym)Cl(L)]PF6 (5–8) were stable in aqueous environments, in contrast to the rapid degradation observed for the co-studied rhodium(III) (9–12) and iridium(III) (13–16) [M(η5-Cp*)Cl(L)]PF6 complexes; L = ethane-1,2-diamine-based Schiff bases (L1–L4) bearing two terminal PAH substituents 2-naphtyl (for L1), 9-anthracenyl (for L2), 9-phenanthrenyl (L3) or 1-pyrenyl (L4); pcym = 1-methyl-4-(propan-2-yl)benzene (p-cymene), Cp* = pentamethylcyclopentadienyl. Biological testing demonstrated that 1–8 possess significant antiproliferative activity against various lung cancer cell lines, including those resistant to cisplatin, with Os(II) complex 5 showing the highest cytotoxicity. Treatment with these complexes led to the activation of stress-related gene pathways, including unconventional endoplasmic reticulum stress, apoptotic signalling, and mitochondrial membrane depolarization. Activation of p21/GADD45A pathway indicates DNA-damage response, as well. Notably, these complexes did not induce significant inflammatory responses, a notable advantage over cisplatin. The results highlight the potential of Ru and Os half-sandwich complexes as alternative metallodrugs, capable of overcoming platinum resistance and minimizing inflammatory side effects. This study suggests that these compounds could serve as a promising class of anticancer agents for future clinical development.
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
30104 - Pharmacology and pharmacy
Result continuities
Project
<a href="/en/project/NU22-08-00236" target="_blank" >NU22-08-00236: Pre-clinical study of non-platinum metalodrugs for lung cancer therapy</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
European Journal of Medicinal Chemistry
ISSN
0223-5234
e-ISSN
1768-3254
Volume of the periodical
297
Issue of the periodical within the volume
November 2025
Country of publishing house
FR - FRANCE
Number of pages
16
Pages from-to
"117970"
UT code for WoS article
001540981800001
EID of the result in the Scopus database
2-s2.0-105011059555