Anticancer Potential of Diruthenium Complexes with Bridging Hydrocarbyl Ligands from Bioactive Alkynols

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F23%3A73621733" target="_blank" >RIV/61989592:15310/23:73621733 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15640/23:73621733

Výsledek na webu

<a href="https://pubs.acs.org/doi/epdf/10.1021/acs.inorgchem.3c01731" target="_blank" >https://pubs.acs.org/doi/epdf/10.1021/acs.inorgchem.3c01731</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.inorgchem.3c01731" target="_blank" >10.1021/acs.inorgchem.3c01731</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Anticancer Potential of Diruthenium Complexes with Bridging Hydrocarbyl Ligands from Bioactive Alkynols

Popis výsledku v původním jazyce

Diruthenacyclopentenone complexes of the general composition [Ru2Cp2(CO)(2){mu-eta(1):eta(3)-CH=C(C(OH)( R))C(=O)}] (2a- c; Cp = eta(5)-C5H5) were synthesized in 94-96% yields from the reactions of [Ru2Cp2(CO)(2){mu-eta(1):eta(3)-C(Ph)=C(Ph)C(=O)}] (1) with 1-ethynylcyclopentanol, 17 alpha-ethynylestradiol, and 17-ethynyltestosterone, respectively, in toluene at reflux. Protonation of 2a-c by HBF4 afforded the corresponding allenyl derivatives [Ru2Cp2(CO)(3){mu-eta(1):eta(2)-CH=C=R}]BF4 (3a-c) in 85-93% yields. All products were thoroughly characterized by elemental analysis, mass spectrometry, and IR, UV- vis, and nuclear magnetic resonance spectroscopy. Additionally, 2a and 3a were investigated by cyclic voltammetry, and the single-crystal diffraction method was employed to establish the X-ray structures of 2b and 3a. The cytotoxicity in vitro of 2b and 3a-c was evaluated against nine human cancer cell lines (A2780, A2780R, MCF-7, HOS, A549, PANC-1, Caco-2, PC-3, and HeLa), while the selectivity was assessed on normal human lung fibroblast (MRC-5). Overall, complexes exert stronger cytotoxicity than cisplatin, and 3b (comprising 17 alpha-estradiol derived ligand) emerged as the best-performing complex. Inductively coupled plasma mass spectrometry cellular uptake studies in A2780 cells revealed a higher level of internalization for 3b and 3c compared to 2b, 3a, and the reference compound RAPTA-C. Experiments conducted on A2780 cells demonstrated a noteworthy impact of 3a and 3b on the cell cycle, leading to the majority of the cells being arrested in the G0/G1 phase. Moreover, 3a moderately induced apoptosis and oxidative stress, while 3b triggered autophagy and mitochondrial membrane potential depletion.

Název v anglickém jazyce

Anticancer Potential of Diruthenium Complexes with Bridging Hydrocarbyl Ligands from Bioactive Alkynols

Popis výsledku anglicky

Diruthenacyclopentenone complexes of the general composition [Ru2Cp2(CO)(2){mu-eta(1):eta(3)-CH=C(C(OH)( R))C(=O)}] (2a- c; Cp = eta(5)-C5H5) were synthesized in 94-96% yields from the reactions of [Ru2Cp2(CO)(2){mu-eta(1):eta(3)-C(Ph)=C(Ph)C(=O)}] (1) with 1-ethynylcyclopentanol, 17 alpha-ethynylestradiol, and 17-ethynyltestosterone, respectively, in toluene at reflux. Protonation of 2a-c by HBF4 afforded the corresponding allenyl derivatives [Ru2Cp2(CO)(3){mu-eta(1):eta(2)-CH=C=R}]BF4 (3a-c) in 85-93% yields. All products were thoroughly characterized by elemental analysis, mass spectrometry, and IR, UV- vis, and nuclear magnetic resonance spectroscopy. Additionally, 2a and 3a were investigated by cyclic voltammetry, and the single-crystal diffraction method was employed to establish the X-ray structures of 2b and 3a. The cytotoxicity in vitro of 2b and 3a-c was evaluated against nine human cancer cell lines (A2780, A2780R, MCF-7, HOS, A549, PANC-1, Caco-2, PC-3, and HeLa), while the selectivity was assessed on normal human lung fibroblast (MRC-5). Overall, complexes exert stronger cytotoxicity than cisplatin, and 3b (comprising 17 alpha-estradiol derived ligand) emerged as the best-performing complex. Inductively coupled plasma mass spectrometry cellular uptake studies in A2780 cells revealed a higher level of internalization for 3b and 3c compared to 2b, 3a, and the reference compound RAPTA-C. Experiments conducted on A2780 cells demonstrated a noteworthy impact of 3a and 3b on the cell cycle, leading to the majority of the cells being arrested in the G0/G1 phase. Moreover, 3a moderately induced apoptosis and oxidative stress, while 3b triggered autophagy and mitochondrial membrane potential depletion.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear chemistry

Projekt

<a href="/cs/project/EF16_019%2F0000754" target="_blank" >EF16_019/0000754: Nanotechnologie pro budoucnost</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

INORGANIC CHEMISTRY

ISSN

0020-1669

e-ISSN

1520-510X

Svazek periodika

62

Číslo periodika v rámci svazku

39

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

15875-15890

Kód UT WoS článku

001068475600001

EID výsledku v databázi Scopus

2-s2.0-85174348152