Diruthenacyclopentenone complexes of the general composition [Ru2Cp2(CO)2{μ-η1:η3-CH═C(C(OH)(R))C(═O)}] (2a-c; Cp = η5-C5H5) were synthesized in 94-96% yields from the reactions of [Ru2Cp2(CO)2{μ-η1:η3-C(Ph)═C(Ph)C(═O)}] (1) with 1-ethynylcyclopentanol, 17α-ethynylestradiol, and 17-ethynyltestosterone, respectively, in toluene at reflux. Protonation of 2a-c by HBF4 afforded the corresponding allenyl derivatives [Ru2Cp2(CO)3{μ-η1:η2-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 17α-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.

Bresciani G., Vanco J., Funaioli T., Zacchini S., Malina T., Pampaloni G., et al. (2023). Anticancer Potential of Diruthenium Complexes with Bridging Hydrocarbyl Ligands from Bioactive Alkynols. INORGANIC CHEMISTRY, 62(39), 15875-15890 [10.1021/acs.inorgchem.3c01731].

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

Zacchini S.;
2023

Abstract

Diruthenacyclopentenone complexes of the general composition [Ru2Cp2(CO)2{μ-η1:η3-CH═C(C(OH)(R))C(═O)}] (2a-c; Cp = η5-C5H5) were synthesized in 94-96% yields from the reactions of [Ru2Cp2(CO)2{μ-η1:η3-C(Ph)═C(Ph)C(═O)}] (1) with 1-ethynylcyclopentanol, 17α-ethynylestradiol, and 17-ethynyltestosterone, respectively, in toluene at reflux. Protonation of 2a-c by HBF4 afforded the corresponding allenyl derivatives [Ru2Cp2(CO)3{μ-η1:η2-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 17α-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.
2023
Bresciani G., Vanco J., Funaioli T., Zacchini S., Malina T., Pampaloni G., et al. (2023). Anticancer Potential of Diruthenium Complexes with Bridging Hydrocarbyl Ligands from Bioactive Alkynols. INORGANIC CHEMISTRY, 62(39), 15875-15890 [10.1021/acs.inorgchem.3c01731].
Bresciani G.; Vanco J.; Funaioli T.; Zacchini S.; Malina T.; Pampaloni G.; Dvorak Z.; Travnicek Z.; Marchetti F.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/951013
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