Synthesis, characterization and cytotoxic activity of organoruthenium(II)-halido complexes with 5-chloro-1<i>H</i>-benzimidazole-2-carboxylic acid

Pantić, Darko N.; Mihajlović-Lalić, Ljiljana E.; Aranđelović, Sandra; Radulović, Siniša; Grgurić-Šipka, Sanja

doi:10.1080/00958972.2019.1583332

Cited by 6 publications

(4 citation statements)

References 45 publications

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“…These results are good evidence of the influence of the triphenylphosphine ligand on cellular toxicity. The literature [20][21][22][23] cites many examples of Ru IIarene complexes, without phosphine, with very high IC 50 values in various tumorigenic cell lines. One of the causes that leads to low toxicity of these compounds is the lack of lipophilic groups, decreasing the cellular uptake of these complexes.…”

Section: Biological Anticancer Experimentsmentioning

confidence: 99%

“…However, the half maximal inhibitory concentration (IC 50 ) values in cancer cells for these compounds are generally high (> 100 μM), which is attributed to the high reactivity of these complexes, as a result of the low stability in organic solvents or under physiological conditions. [20][21][22][23] In addition, there are many papers 22,23 which currently report the use of monophosphines or monopyridines as the "X" ligand, resulting in complexes with high toxicity (< 5 μM), thanks to the lipophilicity enhancement of the compounds, when at least one of these molecules is present in their structures. Furthermore, when "L−L" is N−N, [24][25][26] P−P, [27][28][29][30][31][32] N−S, 33,34 N−O, 24,31,32 O−O 24,35,36 donor ligand, a wide range of IC 50 values is obtained.…”

Section: Introductionmentioning

confidence: 99%

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“Half-Sandwich”/RuII Anticancer Complexes Containing Triphenylphosphine and p-Substituted Benzoic Acids

Honorato¹,

Oliveira²,

Leite³

et al. 2020

J. Braz. Chem. Soc.

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Mononuclear and binuclear Ru II /arene/triphenylphosphine complexes with p-substituted benzoic acid derivatives were prepared and characterized. These monocationic complexes of type [Ru(η 6-p-cymene)(PPh 3)L] (L = benzoic acid (1), p-hydroxybenzoic acid (2), p-nitrobenzoic acid (3) and terephthalic acid (4)) were characterized using various techniques, such as nuclear magnetic resonance (NMR) and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry, and the crystal structure of 1, 3 and 4 were determined by X-ray diffraction analysis. The cytotoxicity of the complexes was evaluated, in vitro, against tumorigenic [MDA-MB-231, MCF-7 (breast), A549 (lung) and DU-145 (prostate)] and non-tumorigenic [MCF-10A (breast), MRC-5 (lung) and PNT-2 (prostate)] cells. The binuclear complex (4) was inactive due to its low solubility. Complexes 1, 2 and 3 showed similar cytotoxicity, however, complex 1 presented better selectivity index against MDA-MB-231 than compounds 2 and 3. Cellular ruthenium absorption was explored by inductively coupled plasma mass spectrometry (ICP-MS) analyzing the whole cells and the culture medium. Complementary studies showed that complex 1 inhibited colony formation, induced morphology changes in cells and promoted cell cycle arrest in the Sub-G1 phase for the MDA-MB-231 cells.

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Section: Biological Anticancer Experimentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“Half-Sandwich”/RuII Anticancer Complexes Containing Triphenylphosphine and p-Substituted Benzoic Acids

Honorato¹,

Oliveira²,

Leite³

et al. 2020

J. Braz. Chem. Soc.

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“…However, the complex with the bipy ligand showed better selectivity. In comparison to the classes of ruthenium(II) polypyridyl − and iridium/ruthenium arene − complexes, the ruthenium(II) diphosphine compounds containing mercapto ligands (NS) are more cytotoxic in several cancer cell lines.…”

Section: Results and Discussionmentioning

confidence: 99%

Ruthenium(II) Phosphine/Mercapto Complexes: Their in Vitro Cytotoxicity Evaluation and Actions as Inhibitors of Topoisomerase and Proteasome Acting as Possible Triggers of Cell Death Induction

et al. 2020

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In this paper, a series of new ruthenium complexes of the general formula [Ru(NS)(dpphpy)(dppb)]PF 6 (Ru1−Ru3), where dpphpy = diphenyl-2-pyridylphosphine, NS ligands = 2-thiazoline-2-thiol (tzdt, Ru1), 2-mercaptopyrimidine (pySm, Ru2), and 4,6diamino-2-mercaptopyrimidine (damp, Ru3), and dppb = 1,4-bis(diphenylphosphino)butane, were synthesized and characterized by elemental analysis, spectroscopic techniques (IR, UV/ visible, and 1D and 2D NMR), and X-ray diffraction. In the characterization, the correlation between the phosphorus atoms and their respective aromatic hydrogen atoms of the compounds in the assignment stands outs, by 1 H− 31 P HMBC experiments. The compounds show anticancer activities against A549 (lung) and MDA-MB-231 (breast) cancer cell lines, higher than the clinical drug cisplatin. All of the complexes are more cytotoxic against the cancer cell lines than against the MRC-5 (lung) and MCF-10A (breast) nontumorigenic human cell lines. For A549 tumor cells, cell cycle analysis upon treatment with Ru2 showed that it inhibits the mitotic phase because arrest was observed in the Sub-G1 phase. Additionally, the compound induces cell death by an apoptotic pathway in a dose-dependent manner, according to annexin V-PE assay. The multitargeted character of the compounds was investigated, and the biomolecules were DNA, topoisomerase IB, and proteasome, as well as the fundamental biomolecule in the pharmacokinetics of drugs, human serum albumin. The experimental results indicate that the complexes do not target DNA in the cells. At low concentrations, the compounds showed the ability to partially inhibit the catalytic activity of topoisomerase IB in the process of relaxation of the DNA plasmid. Among the complexes assayed in cultured cells, complex Ru3 was able to diminish the proteasomal chymotrypsin-like activity to a greater extent.

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“…cellular shrinkage, nuclear fragmentation and condensation as compared to the untreated cells suggested cellular apoptosis. 32 The MTT assay showed that all synthesized complexes significantly (p<0.001) induce the anti-proliferative and cytotoxicity effects on THP-1 cells after 24h exposure Figure 6. (Figure 8).…”

Section: Biological Activitiesmentioning

confidence: 96%

Synthesis, Characterization and Cytotoxicity Evaluation on Monocytic Cell Line THP1 of Ru(II) Complexes with 1, 2-Disubstituted Benzimidazoles

Singh¹,

Katheria²,

Jafri³

et al. 2019

JBCC

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INTRODUCTION: The medicinal value of cis-Platin has led to the discovery of alternative metal complexes with better medicinal properties. 1 Ruthenium based metal complexes have novel anticancer properties. 2 Ruthenium complexes with ligands containing groups as amines, imines and imidazoles such as [ImH][trans-Ru(III)Cl 4 (dmso-S)(Im)](NAMI-A; Im = Imidazole, dmso = dimethylsulfoxide) and [IndH][trans-Ru(III) Cl 4 (Ind) 2 ] (KP1019; Ind = indazole), have successfully completed phase-1clinical trials and are scheduled to enter phase 2 trials in the near future. 14,3,4 In addition, benzimidazole derivatives show significant antiinflammatory, antioxidant, gastroprotective and antiparasitic activities. Therefore, large number of its metal complexes has been synthesized and applied in urea recognition, DNA binding, catalysis and chemical sensors in biological systems. 5,6 With bisbenzimidazole derivatives, ruthenium compounds exhibit powerful cytotoxicity against ovarian carcinoma cells, which creates the underlying mechanism of anticancer functions. 7,8 Ruthenium is an alternative to platinum, because of accessible oxidation states and less toxic than platinum counterpart, which makes them significant for anticancer activities under physiological conditions. 9,10 This is due to the ability of ruthenium to mimic iron in the binding to biological molecules, such as albumin and transferrin, although platinum drugs can also bind to the proteins. 11 Since rapidly dividing cells, such as cancerous cells, more demand for iron, transferrin receptors are overexpressed, so that ruthenium-based medicines can be delivered more effectively to cancerous cells. 12 Furthermore, activation by "reduction" mechanisms may be responsible for toxicity of some ruthenium compounds. 13 In the last two decades, a new approach to the treatment of cancer, known as Targeted Medicine and Targeting Cellular Signaling Path of Cancer Cells, starts producing highly effective cancer treatment with very little serious side effects. 15, 16 Some of them, e.g. Imatinib mesylate and Erlotinib hydrochloride have

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Synthesis, characterization and cytotoxic activity of organoruthenium(II)-halido complexes with 5-chloro-1H-benzimidazole-2-carboxylic acid

Cited by 6 publications

References 45 publications

“Half-Sandwich”/RuII Anticancer Complexes Containing Triphenylphosphine and p-Substituted Benzoic Acids

“Half-Sandwich”/RuII Anticancer Complexes Containing Triphenylphosphine and p-Substituted Benzoic Acids

Ruthenium(II) Phosphine/Mercapto Complexes: Their in Vitro Cytotoxicity Evaluation and Actions as Inhibitors of Topoisomerase and Proteasome Acting as Possible Triggers of Cell Death Induction

Synthesis, Characterization and Cytotoxicity Evaluation on Monocytic Cell Line THP1 of Ru(II) Complexes with 1, 2-Disubstituted Benzimidazoles

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