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Article Dans Une Revue Inorganic Chemistry Année : 2020

Synthesis, Characterization, Cytotoxic Activity, and Metabolic Studies of Ruthenium(II) Polypyridyl Complexes Containing Flavonoid Ligands

Résumé

Four novel monocationic Ru(II) polypyridyl complexes were synthesized with the general formula [Ru(DIP)2flv]X, where DIP is 4,7-diphenyl-1,10-phenanthroline, flv stands for the flavonoid ligand (5-hydroxyflavone in [Ru(DIP)2(5-OHF)](PF6), genistein in [Ru(DIP)2(gen)](PF6), chrysin in [Ru(DIP)2(chr)](OTf), and morin in [Ru(DIP)2(mor)](OTf)), and X is the counterion, PF6−, and OTf ̅ (triflate, CF3SO3̅), respectively. Following the chemical characterization of the complexes by 1H and 13C NMR, mass spectrometry, and elemental analysis, their cytotoxicity was tested against several cancer cell lines. The most promising complex, [Ru(DIP)2(gen)](PF6), was further investigated for its biological activity. Metabolic studies revealed that this complex severely impaired mitochondrial respiration and glycolysis processes, contrary to its precursor, Ru(DIP)2Cl2, which showed a prominent effect only on the mitochondrial respiration. In addition, its preferential accumulation in MDA-MB-435S cells (a human melanoma cell line previously described as mammary gland/breast; derived from metastatic site: pleural effusion), which are used for the study of metastasis, explained the better activity in this cell line compared to MCF-7 (human, ductal carcinoma).

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Dates et versions

hal-02513155 , version 1 (20-03-2020)

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Alexandra-Cristina Munteanu, Anna Notaro, Marta Jakubaszek, Joseph Cowell, Mickaël Tharaud, et al.. Synthesis, Characterization, Cytotoxic Activity, and Metabolic Studies of Ruthenium(II) Polypyridyl Complexes Containing Flavonoid Ligands. Inorganic Chemistry, 2020, ⟨10.1021/acs.inorgchem.9b03562⟩. ⟨hal-02513155⟩
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