Journal
INORGANIC CHEMISTRY
Volume 59, Issue 7, Pages 4424-4434Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.inorgchem.9b03562
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Funding
- ERC [GA 681679]
- program Investissements d'Avenir
- ANR [ANR-10-IDEX-0001-02 PSL]
- 500 MHz NMR spectrometer of Chimie ParisTech in the framework of the SESAME equipment project
- IPGP multidisciplinary program PARI
- Region Ile-de-France SESAME [12015908]
- Carol Davila University of Medicine and Pharmacy - Ministry of Research and Innovation within PNCDI III [23PFE/17.10.2018]
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Four novel monocationic Ru(II) polypyridyl complexes were synthesized with the general formula [Ru(DIP)(2)fly]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, CF3SO3-), respectively. Following the chemical characterization of the complexes by H-1 and C-13 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)(2)Cl-2, 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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