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

Diruthenacyclopentenone complexes of the general composition [Ru 2 Cp 2 (CO) 2 {μ-η 1 :η 3 -CH═C(C(OH)(R))C(═O)}] ( 2a - c ; Cp = η 5 -C 5 H 5 ) were synthesized in 94-96% yields from the reactions of [Ru 2 Cp 2 (CO) 2 {μ-η 1 :η 3 -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 HBF 4 afforded the corresponding allenyl derivatives [Ru 2 Cp 2 (CO) 3 {μ-η 1 :η 2 -CH═C═R}]BF 4 ( 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.