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

被引：45

作者：

Munteanu, Alexandra Cristina ^{[2
]}

Notaro, Anna ^{[1
]}

Jakubaszek, Marta ^{[1
]}

Cowell, Joseph ^{[1
]}

Tharaud, Mickael ^{[3
]}

Goud, Bruno ^{[4
]}

Uivarosi, Valentina ^{[2
]}

Gasser, Gilles ^{[1
]}

机构：

[1] PSL Univ, Chim ParisTech, CNRS, Inst Chem Life & Hlth Sci,Lab Inorgan Chem Biol, F-75005 Paris, France

[2] Carol Davila Univ Med & Pharm, Fac Pharm, Dept Gen & Inorgan Chem, Bucharest 020956, Romania

[3] Univ Paris, Inst Phys Globe Paris, CNRS, F-75005 Paris, France

[4] PSL Univ, Inst Curie, CNRS UMR 144, Paris, France

来源：

INORGANIC CHEMISTRY | 2020年 / 59卷 / 07期

关键词：

PHASE-I; BIOLOGICAL EVALUATION; ANTICANCER AGENT; CELLULAR UPTAKE; GENISTEIN; CANCER; KP1019; DRUG; PHOTOSENSITIZERS; MECHANISMS;

D O I：

10.1021/acs.inorgchem.9b03562

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

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).

引用

页码：4424 / 4434

页数：11

共 69 条

[1] Thirty Years of the Drug Candidate NAMI-A and the Myths in the Field of Ruthenium Anticancer Compounds: A Personal Perspective [J].