Synthesis, characterization and biological evaluation of cationic organoruthenium(<scp>ii</scp>) fluorene complexes: influence of the nature of the counteranion

Haghdoost, Mohammad Mehdi; Golbaghi, Golara; Guard, Juliette; Sielanczyk, Sarah; Patten, Shunmoogum A.; Castonguay, Annie

doi:10.1039/c9dt00143c

Cited by 16 publications

(17 citation statements)

References 51 publications

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“…The dark and light IC 50 values of the complexes against various cancer cell lines are listed in Table S5. The reduced cytotoxicity of cisplatin was probably due to the short‐term incubation (4 h) [42,45–47] . Upon 465 nm light irradiation, Ir1 – Ir3 exhibited much higher photo‐cytotoxicity index (PI, PI=IC 50 dark /IC 50 light ) than 5‐ALA (PI=23–793 for Ir1 – Ir3 vs. 22.37–29.63 for 5‐ALA) against various cancer cell lines.…”

Section: Resultsmentioning

confidence: 99%

Highly Efficient Ir(III)‐Coumarin Photo‐Redox Catalyst for Synergetic Multi‐Mode Cancer Photo‐Therapy

Huang

Fan

Xie

et al. 2021

Chemistry A European J

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Four photo‐catalysts of the general formula [Ir(CO6/ppy)2(L)]Cl where CO6=coumarin 6 (Ir1–Ir3), ppy=2‐phenylpyridine (Ir4), L=4′‐(3,5‐di‐tert‐butylphenyl)‐2,2′ : 6′,2′′‐terpyridine (Ir1), 4′‐(3,5‐bis(trifluoromethyl)phenyl)‐2,2′ : 6′,2′′‐terpyridine (Ir2 and Ir4), and 4‐([2,2′ : 6′,2′′‐terpyridin]‐4′‐yl)‐N,N‐dimethylaniline (Ir3) were synthesized and characterized. These photostable photo‐catalysts (Ir1–Ir3) showed strong visible light absorption between 400–550 nm. Upon light irradiation (465 and 525 nm), Ir1–Ir3 generated singlet oxygen and induced rapidly photo‐catalytic oxidation of cellular coenzymes NAD(P)H. Ir1–Ir3 showed time‐dependent cellular uptake with excellent intracellular retention efficiency. Upon green light irradiation (525 nm), Ir2 provided a much higher photo‐index (PI=793) than the clinically used photosensitizer, 5‐aminolevulinicacid (5‐ALA, PI>30) against HeLa cancer cells. The observed necro‐apoptotic anticancer activity of Ir2 was due to the Ir2 triggered photo‐induced intracellular redox imbalance (by NAD(P)H oxidation and ROS generation) and change in the mitochondrial membrane potential. Remarkably, Ir2 showed in vivo photo‐induced catalytic anticancer activity in mouse models.

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Section: Resultsmentioning

confidence: 99%

Highly Efficient Ir(III)‐Coumarin Photo‐Redox Catalyst for Synergetic Multi‐Mode Cancer Photo‐Therapy

Huang

Fan

Xie

et al. 2021

Chemistry A European J

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“…Cellular ruthenium levels of each complex appeared to depend on their respective lipophilicity, in agreement with previous reports demonstrating that more hydrophobic systems have a greater affinity for the cell membrane. 47 For instance, lipophilic counterion-containing compounds 2 and 3 (BPh 4 -) displayed the highest ruthenium cellular uptake (3 > 2 > 1, 4, 5).…”

Section: Resultsmentioning

confidence: 99%

“…63,64 Also, the zebrafish embryo assay has previously been reported to be a suitable phenotype-based screening method to assess the in vivo toxicity of ruthenium complexes. 47,[65][66][67] Because of their greater in vitro cytotoxicity in T47D cells compared to that of the currently used chemotherapeutic agent cis-platin, complexes 2 and 3 were selected for an in vivo toxicity assessment using the zebrafish embryo assay. Hatching rates, survival rates and phenotype changes of the zebrafish embryos treated with 12.5 μM of each compound were determined at 24, 48, 72 and 96 h post fertilization (hpf) ( Figure 6).…”

Section: Resultsmentioning

confidence: 99%

Organoruthenium(II) Complexes Bearing an Aromatase Inhibitor: Synthesis, Characterization, in Vitro Biological Activity and in Vivo Toxicity in Zebrafish Embryos

et al. 2019

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Third-generation aromatase inhibitors such as anastrozole (ATZ) and letrozole (LTZ) are widely used to treat estrogen receptor-positive ER+ breast cancers in postmenopausal women. Investigating their ability to coordinate metals could lead to the emergence of a new category of anticancer drug candidates with a broader spectrum of pharmacological activities. In this study, a series of ruthenium (II) arene complexes bearing the aromatase inhibitor anastrozole was synthesized and characterized. Among these complexes, [Ru(η 6-C 6 H 6)(PPh 3)(η 1-ATZ)Cl]BPh 4 (3) was found to be the most stable in cell culture media, to lead to the highest cellular uptake and in vitro cytotoxicity in two ER+ human breast cancer cell lines (MCF7 and T47D), and to induce a decrease in aromatase activity in H295R cells. Exposure of zebrafish embryos to complex 3 (12.5 μM) did not lead to noticeable signs of toxicity over 96 h, making it a suitable candidate for further in vivo investigations.

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“…The anionic Ru(III) species 3, Na[trans-RuCl 4 ATZ(DMSO)], was also prepared by allowing Na[trans-RuCl 4 (DMSO) 2 ] to react with anastrozole in acetone overnight at room temperature (56% yield). Keeping in mind that the anticancer properties of metal complexes often vary with their lipophilicity [27,54], the sodium counterion in the structure of 3 was replaced with a more lipophilic cation. Complex 5, PPh 4 [trans-RuCl 4 ATZ(DMSO)], was then obtained (70% yield) by allowing a methanol solution of compound 3 to react with PPh 4 Cl for 4 h at room temperature.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and biological assessment of a ruthenium(II) cyclopentadienyl complex in breast cancer cells and on the development of zebrafish embryos

Golbaghi

Pitard

Lucas

et al. 2020

European Journal of Medicinal Chemistry

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Ruthenium-based complexes currently attract great attention as they hold promise to replace platinum-based drugs as a first line cancer treatment. Whereas ruthenium arene complexes are some of the most studied species for their potential anticancer properties, other types of ruthenium complexes have been overlooked for this purpose. Here, we report the synthesis and characterization of Ru(II) cyclopentadienyl (Cp), Ru(II) cyclooctadienyl (COD) and Ru(III) complexes bearing anastrozole or letrozole ligands, third-generation aromatase inhibitors currently used to treat estrogen receptor-positive (ER+) breast cancer. Among these complexes, Ru(II)Cp 2 was the only species found to be stable in DMSO and in cell culture media and as a result, the only complex for which the in vitro and in vivo biological activities were investigated. Unlike anastrozole alone, complex 2 was considerably cytotoxic in vitro (IC50 values < 1μM) in human Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Synthesis, characterization and biological evaluation of cationic organoruthenium(ii) fluorene complexes: influence of the nature of the counteranion

Abstract: In this study, the in vitro antiproliferative activity and the in vivo toxicity of ruthenium arene complexes bearing fluorene bidentate ligands was assessed in human breast cancer cells and on the development of zebrafish embryos, respectively.

Cited by 16 publications

References 51 publications

Highly Efficient Ir(III)‐Coumarin Photo‐Redox Catalyst for Synergetic Multi‐Mode Cancer Photo‐Therapy

Highly Efficient Ir(III)‐Coumarin Photo‐Redox Catalyst for Synergetic Multi‐Mode Cancer Photo‐Therapy

Organoruthenium(II) Complexes Bearing an Aromatase Inhibitor: Synthesis, Characterization, in Vitro Biological Activity and in Vivo Toxicity in Zebrafish Embryos

Synthesis and biological assessment of a ruthenium(II) cyclopentadienyl complex in breast cancer cells and on the development of zebrafish embryos

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