Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N-indolyl derivative as a prospective anticancer agent
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F24%3A73625117" target="_blank" >RIV/61989592:15310/24:73625117 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15640/24:73625117
Result on the web
<a href="https://pubs.rsc.org/en/content/articlelanding/2024/qi/d4qi00096j" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2024/qi/d4qi00096j</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/d4qi00096j" target="_blank" >10.1039/d4qi00096j</a>
Alternative languages
Result language
angličtina
Original language name
Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N-indolyl derivative as a prospective anticancer agent
Original language description
We conducted a systematic study on the reactivity of [Ru2Cp2(CO)(4)] (Cp = eta(5)-C5H5) with isocyanides and the subsequent methylation reaction to produce [Ru2Cp2(CO)(2)(mu-CO){mu-CNMe(R)}]+ complexes as CF3SO3- salts, [2a-h]+ [R = Me, cyclohexyl (Cy), 2,6-C6H3Me2 (Xyl), 1H-indol-5-yl, 2-naphthyl, 4-C6H4OMe, (S)-CHMe(Ph), CH2Ph (Bn)]. The resulting products, including five novel ones, underwent structural characterization by IR and multinuclear NMR spectroscopy, with five of them further confirmed via single crystal X-ray diffraction. Compounds [2a-e,h]CF(3)SO(3 )exhibit appreciable water solubility, substantial amphiphilic character and outstanding stability in physiological-like solutions (negligible degradation after 72 hours in DMEM at 37(degrees)C). Representative complexes [2b](+) and [2c](+ )were additionally characterized through cyclic voltammetry in CH2Cl2 and in aqueous phosphate buffer solution. Compounds [2a-d]CF3SO3 were assessed for in vitro cytotoxicity against A2780, A2080R and MCF-7 human cancer cell lines, and [2a-c]CF3SO3 revealed significant-to-moderate cytotoxicity, outperforming cisplatin in several cases. The most favourable IC50 values were observed for [2d]CF3SO3, ranging from 3.7 to 13.0 mu M. Experiments on the noncancerous human cell line MRC-5 highlighted a reasonable selectivity for [2b-d]CF3SO3, with the highest selectivity indexes (SI) calculated as 10.1 (ratio of IC(50 )on MRC-5/IC50 on A2780) and 8.5 (ratio of IC50 on MRC-5/IC(50 )on A2780R) for [2d]CF3SO3. Subsequently, [2d]CF3SO3 was tested across a panel of HOS, A549, PANC1, CaCo2, PC3 and HeLa cancer cells, showing variable cytotoxicity with IC50 values in the range of 9.7 to 20.3 mu M. The cellular effects of [2d](+ )on A2780 cells were investigated using flow cytometry assays, focusing on the cell cycle modification, time-resolved cellular uptake, intracellular ROS production, mitochondrial membrane depolarization, induction of cell death through apoptosis, activation of caspases 3/7 and induction of autophagy. Overall, the results suggest a diphasic mechanism of action for [2d]+, inducing metabolic stress and arresting proliferation in the first/fast phase, followed by the induction of apoptosis and autophagy in the second/slower phase.
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
10402 - Inorganic and nuclear chemistry
Result continuities
Project
<a href="/en/project/EF16_019%2F0000754" target="_blank" >EF16_019/0000754: Nanotechnologies for Future</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
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
Inorganic Chemistry Frontiers
ISSN
2052-1545
e-ISSN
2052-1553
Volume of the periodical
11
Issue of the periodical within the volume
10
Country of publishing house
GB - UNITED KINGDOM
Number of pages
22
Pages from-to
"2841 "- 2862
UT code for WoS article
001182048000001
EID of the result in the Scopus database
2-s2.0-85187718236