Ligand Design for N, O- or N, N-Pyrazolone-Based Hydrazones Ruthenium(II)-Arene Complexes and Investigation of Their Anticancer Activity.
Riccardo PettinariFabio MarchettiCorrado Di NicolaClaudio PettinariAgustı N GalindoRiccardo PetrelliLoredana CappellacciMassimiliano CuccioloniLaura BonfiliAnna Maria EleuteriMaria de Fátima C Guedes da SilvaArmando J L PombeiroPublished in: Inorganic chemistry (2018)
Three pyrazolone-based hydrazone ligands HL' (HL' in general; in detail, HL1 = 2-((5-hydroxo-3-methyl-1-phenyl-1 H-pyrazol-4-yl)(phenyl)methylene)-1-(2,4-nitrophenyl)hydrazine, HL2 = 2-((5-hydroxo-3-methyl-1-phenyl-1 H-pyrazol-4-yl) (phenyl)methylene)-1-(4-nitrophenyl)hydrazine, and HL3 = 2-((5-hydroxo-3-methyl-1-phenyl-1 H-pyrazol-4-yl)(phenyl)methylene)-1-(pyridin-2-yl)hydrazine) have been prepared starting from 4-benzoyl-3-methyl-1-phenyl-1 H-pyrazol-5(4 H)-one and fully characterized in the solid state and solution, where the existing tautomeric forms were identified by taking advantage of natural abundance 1H-15N coupling in {1H-15N}-HSQC and {1H-15N}-HMBC NMR spectroscopy. Then, six half-sandwich arene-ruthenium(II) derivatives (arene = hexamethylbenzene and p-cymene) of composition [(arene)Ru(L')Cl] have been synthesized and fully characterized by IR, 1H, and 13C NMR spectroscopy, electrospray ionization mass spectrometry, elemental analysis, and density functional theory calculations. The crystal structures of three complexes, together with the E configurational isomer (with respect to the C═N double bond) of the free proligand HL2 and the zwitterionic proligand HL3 were determined by X-ray analysis. The anionic ligands L1 and L2 were found bonded to ruthenium in the N,O-form, while L3 coordinates the metal in the N,N-form affording five-membered chelating rings. The cytotoxicity of the complexes was evaluated against human breast adenocarcinoma cells (MCF-7 and MCF-7CR), as well as against nontumorigenic human breast (MCF-10A) cells and compared to the free ligand and cisplatin.
Keyphrases
- density functional theory
- induced apoptosis
- endothelial cells
- mass spectrometry
- solid state
- breast cancer cells
- molecular dynamics
- cell cycle arrest
- water soluble
- high resolution
- oxidative stress
- cell death
- magnetic resonance
- endoplasmic reticulum stress
- pluripotent stem cells
- microbial community
- capillary electrophoresis
- structure activity relationship