Novel NHC-coordinated ruthenium(II) arene complexes achieve synergistic efficacy as safe and effective anticancer therapeutics

Chen, Chao; Chang, Xu; Li, Tongyu; Lu, Shu‐Ling; Luo, Fangzhou; Wang, Hangxiang

doi:10.1016/j.ejmech.2020.112605

Cited by 44 publications

(34 citation statements)

References 44 publications

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“…From the results compiled in Figure 10, we concluded that, unlike HL4, all its metal complexes increase ROS production, with the Ir complex inducing the greatest effect. ROS levels can be modulated by several reported mechanisms such as binding of the metal complex to GSH, thioredoxin reductase inhibition, catalytic oxidation of NADH and NADPH [36,136,137].…”

Section: Intracellular Ros Generationmentioning

confidence: 99%

Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal

et al. 2021

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An important challenge in the field of anticancer chemotherapy is the search for new species to overcome the resistance of standard drugs. An interesting approach is to link bioactive ligands to metal fragments. In this work, we have synthesized a set of p-cymene-Ru or cyclopentadienyl-M (M = Rh, Ir) complexes with four chrysin-derived pro-ligands with different -OR substituents at position 7 of ring A. The introduction of a piperidine ring on chrysin led to the highly cytotoxic pro-ligand HL4 and its metal complexes L4-M (SW480 and A549 cell lines, cytotoxic order: L4-Ir > L4-Ru ≈ L4-Rh). HL4 and its complexes induce apoptosis and can overcome cis-platinum resistance. However, HL4 turns out to be more cytotoxic in healthy than in tumor cells in contrast to its metal complexes which displayed higher selectivity than cisplatin towards cancer cells. All L4-M complexes interact with double stranded DNA. Nonetheless, the influence of the metal is clear because only complex L4-Ir causes DNA cleavage, through the generation of highly reactive oxygen species (1O2). This result supports the hypothesis of a potential dual mechanism consisting of two different chemical pathways: DNA binding and ROS generation. This behavior provides this complex with a great effectivity in terms of cytotoxicity.

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Section: Intracellular Ros Generationmentioning

confidence: 99%

Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal

et al. 2021

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“…Cell cycle arrest at G1/S transition as a consequence of treatment with ruthenium( ii ) complexes has been reported in non-small cell lung cancer (A549), 15 urinary bladder carcinoma (T-24), 33 hepatocellular carcinoma (HepG2), 34 and human ovarian A2780 cancer cells. 35…”

Section: Discussionmentioning

confidence: 99%

Ruthenium(ii) complex containing cinnamic acid derivative inhibits cell cycle progression at G0/G1 and induces apoptosis in melanoma cells

et al. 2022

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“…(Figure 2g). [28] Likewise, arene ruthenium complexes that includes bidentate chelating ligands with N, O donor atoms have been investigated for their anticancer properties. [29] Further, it is worth to note that the modification of organo ruthenium complexes to nanomaterials would increase the cytotoxicity toward human cancer cell lines due to enhanced permeability across the cell membrane.…”

Section: Introductionmentioning

confidence: 99%

Assessment of antiproliferative activity of new half‐sandwich arene Ru (II) furylbenzhydrazone complexes

Prabaharan

Ramesh

Umapathy

et al. 2021

Applied Organom Chemis

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The study attempts in finding an effective anticancer activity of six new arene ruthenium (II) complexes possessing the composition of [(η 6 -arene)Ru(L)Cl] (arene = benzene (1-3) /p-cymene (4-6); L = 2-furyl methyl benzhydrazones).Elemental analysis, Fourier transform infrared spectroscopy (FT-IR), UV-vis, nuclear magnetic resonance (NMR), and high resolution mass spectrometry (HR-MS) techniques were utilized to study the synthesized complexes. The single crystal X-ray crystallography validated the bidentate mode of coordination of the benzhydrazone ligand and pseudo-octahedral geometry around ruthenium ion. MTT assay has been performed to assess the in vitro growth of cancer cell inhibition ability of all the complexes against MCF-7(breast carcinoma), HuH-7 (hepatocellular carcinoma), and HeLa (cervical cancer), along with non-cancerous L132 (human lung epithelium) cell lines. It has been found that all the six complexes exhibit good to excellent cytotoxicity toward the cancer cell lines tested with low IC 50 values compared to cisplatin. Among the synthesized complexes, complex 6 shows potential cytotoxicity against all the cancer cell lines. The observed higher cytotoxicity of the complex 6 may be due to the electron donating methoxy group of the ligand and hydrophobic character of arene moiety. Eventually, the staining techniques such as AO-EB, HOECHST 33342, RH-123, and reactive oxygen species (ROS) establish that all the complexes bring about cell death via apoptosis. The present research results emphasize the more possibility to promote potential arene ruthenium anticancer agents.

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Novel NHC-coordinated ruthenium(II) arene complexes achieve synergistic efficacy as safe and effective anticancer therapeutics

Cited by 44 publications

References 44 publications

Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal

Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal

Ruthenium(ii) complex containing cinnamic acid derivative inhibits cell cycle progression at G0/G1 and induces apoptosis in melanoma cells

Assessment of antiproliferative activity of new half‐sandwich arene Ru (II) furylbenzhydrazone complexes

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