Half-sandwich Ru(η6-p-cymene) complexes featuring pyrazole appended ligands: Synthesis, DNA binding and in vitro cytotoxicity

Huang, Yen-Chung; Haribabu, Jebiti; Chien, Ching-Ming; Sabapathi, Gopal; Chou, Chia-Man; Karvembu, Ramasamy; Venuvanalingam, Ponnambalam; Ching, Wei-Min; Tsai, M.‐H.; Hsu, Sodio C. N.

doi:10.1016/j.jinorgbio.2019.02.012

Cited by 33 publications

(11 citation statements)

References 83 publications

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“…Anticancer agents are complexes known to show activity by binding to DNA either covalently or noncovalently. Noncovalent interactions occur through an intercalative, an electrostatic, or a groove (minor or major) mode of binding, while in covalent interactions, labile ligand of complexes is exchanged by the N donor atom of the nucleotide in the base pairs of DNA . The intercalative mode of binding of the present complexes with CT DNA was confirmed by UV–vis absorption, emission, and viscosity techniques, and the order of binding strength was found to be 3 > 1 > 2 .…”

Section: Resultsmentioning

confidence: 69%

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Synthesis of Palladium(II) Complexes via Michael Addition: Antiproliferative Effects through ROS-Mediated Mitochondrial Apoptosis and Docking with SARS-CoV-2

et al. 2020

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Metal complexes have numerous applications in the current era, particularly in the field of pharmaceutical chemistry and catalysis. A novel synthetic approach for the same is always a beneficial addition to the literature. Henceforth, for the first time, we report the formation of three new Pd(II) complexes through the Michael addition pathway. Three chromone-based thiosemicarbazone ligands (SVSL1–SVSL3) and Pd(II) complexes ( 1 – 3 ) were synthesized and characterized by analytical and spectroscopic tools. The Michael addition pathway for the formation of complexes was confirmed by spectroscopic studies. Distorted square planar structure of complex 2 was confirmed by single-crystal X-ray diffraction. Complexes 1 – 3 were subjected to DNA- and BSA-binding studies. The complex with cyclohexyl substituent on the terminal N of thiosemicarbazone ( 3 ) showed the highest binding efficacy toward these biomolecules, which was further understood through molecular docking studies. The anticancer potential of these complexes was studied preliminarily by using MTT assay in cancer and normal cell lines along with the benchmark drugs (cisplatin, carboplatin, and gemcitabine). It was found that complex 3 was highly toxic toward MDA-MB-231 and AsPC-1 cancer cells with IC 50 values of 0.5 and 0.9 μM, respectively, and was more efficient than the standard drugs. The programmed cell death mechanism of the complexes in MDA-MB-231 cancer cells was confirmed. Furthermore, the complexes induced apoptosis via ROS-mediated mitochondrial signaling pathway. Conveniently, all the complexes showed less toxicity (≥50 μM) against MCF-10a normal cell line. Molecular docking studies were performed with VEGFR2, EGFR, and SARS-CoV-2 main protease to illustrate the binding efficiency of the complexes with these receptors. To our surprise, binding potential of the complexes with SARS-CoV-2 main protease was higher than that with chloroquine and hydroxychloroquine.

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Section: Resultsmentioning

confidence: 69%

“…Complex 3 showed greater binding than the other two complexes. This may be due to the presence of cyclohexyl group in complex 3 in addition to triphenylphosphine, which shows hydrophobic interactions with DNA. , The results and detailed discussion are provided in the Supporting Information (Figures S28–S30 and Table S3).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Palladium(II) Complexes via Michael Addition: Antiproliferative Effects through ROS-Mediated Mitochondrial Apoptosis and Docking with SARS-CoV-2

et al. 2020

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“…Absorption studies are a useful technique deployed to predict the binding efficacy of compounds with CT DNA [ 46 ]. Figure 2 a and Figure S3 depicts the absorption spectra of the Zn(II) complexes with and without CT DNA.…”

Section: Resultsmentioning

confidence: 99%

Tris-(2-pyridyl)-pyrazolyl Borate Zinc(II) Complexes: Synthesis, DNA/Protein Binding and In Vitro Cytotoxicity Studies

et al. 2021

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Zn(II) complexes bearing tris[3-(2-pyridyl)-pyrazolyl] borate (Tppy) ligand (1–3) was synthesized and examined by spectroscopic and analytical tools. Mononuclear [TppyZnCl] (1) has a Zn(II) centre with one arm (pyrazolyl-pyridyl) dangling outside the coordination sphere which is a novel finding in TppyZn(II) chemistry. In complex [TppyZn(H2O)][BF4] (2) hydrogen bonding interaction of aqua moiety stabilizes the dangling arm. In addition, solution state behaviour of complex 1 confirms the tridentate binding mode and reactivity studies show the exogenous axial substituents used to form the [TppyZnN3] (3). The complexes (1–3) were tested for their ability to bind with Calf thymus (CT) DNA and Bovine serum albumin (BSA) wherein they revealed to exhibit good binding constant values with both the biomolecules in the order of 104–105 M−1. The intercalative binding mode with CT DNA was confirmed from the UV-Visible absorption, viscosity, and ethidium bromide (EB) DNA displacement studies. Further, the complexes were tested for in vitro cytotoxic ability on four triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, MDA-MB-468, HCC1937, and Hs 578T). All three complexes (1–3) exhibited good IC50 values (6.81 to 16.87 μM for 24 h as seen from the MTS assay) results which indicated that these complexes were found to be potential anticancer agents against the TNBC cells.

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“…Ru(II) complexes with pyridyl-pyrazole ligand have been reported, and the arene complex IX exhibited selective cytotoxic activity against breast cancer cells in vitro. 41 Complex X possessed light-mediated anticancer activity both in vitro and in vivo and has been identified as a potential candidate for PDT. 42 Notably, the pyrazoline-thioamides coordinated to Ru(II) scaffolds XI possessed cytotoxic activity at sub-micromolar concentration ( Chart 1 ).…”

Section: Introductionmentioning

confidence: 99%

“…The cytotoxic effects of Pt(II), Pd(II), Cu(II), , and Au(III) complexes ( VI – VIII ) with pyridyl-pyrazol(in)e ligands have been reported recently, with activity at micromolar concentrations. Ru(II) complexes with pyridyl-pyrazole ligand have been reported, and the arene complex IX exhibited selective cytotoxic activity against breast cancer cells in vitro . Complex X possessed light-mediated anticancer activity both in vitro and in vivo and has been identified as a potential candidate for PDT .…”

Section: Introductionmentioning

confidence: 99%

Photochemical and Photobiological Properties of Pyridyl-pyrazol(in)e-Based Ruthenium(II) Complexes with Sub-micromolar Cytotoxicity for Phototherapy

et al. 2020

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The discovery of new light-triggered prodrugs based on ruthenium (II) complexes is a promising approach for photoactivated chemotherapy (PACT). The light-mediated activation of “strained” Ru(II) polypyridyl complexes resulted in ligand release and produced a ligand-deficient metal center capable of forming covalent adducts with biomolecules such as DNA. Based on the strategy of exploiting structural distortion to activate photochemistry, biologically active small molecules were coordinated to a Ru(II) scaffold to create light-triggered dual-action agents. Thirteen new Ru(II) complexes with pyridyl-pyrazol(in)e ligands were synthesized, and their photochemical reactivity and anticancer properties were investigated. Isomeric bidentate ligands were investigated, where “regular” ligands (where the coordinated nitrogens in the heterocycles are linked by C–C atoms) were compared to “inverse” isomers (where the coordinated nitrogens in the heterocycles are linked by C–N atoms). Coordination of the regular 3-(pyrid-2-yl)-pyrazol(in)es to a Ru(II) bis-dimethylphenanthroline scaffold yielded photoresponsive compounds with promising photochemical and biological properties, in contrast to the inverse 1-(pyrid-2-yl)-pyrazolines. The introduction of a phenyl ring to the 1 N -pyrazoline cycle increased the distortion in complexes and improved ligand release upon light irradiation (470 nm) up to 5-fold in aqueous media. Compounds 1 – 8 , containing pyridyl-pyrazol(in)e ligands, were at least 20–80-fold more potent than the parent pyridyl-pyrazol(in)es, and exhibited biological activity in the dark, with half-maximal inhibitory concentration (IC 50 ) values ranging from 0.2 to 7.6 μM in the HL60 cell line, with complete growth inhibition upon light irradiation. The diversification of coligands and introduction of a carboxylic acid into the Ru(II) complex resulted in compounds 9 – 12 , with up to 146-fold improved phototoxicity indices compared with complexes 1 – 8 .

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Half-sandwich Ru(η6-p-cymene) complexes featuring pyrazole appended ligands: Synthesis, DNA binding and in vitro cytotoxicity

Cited by 33 publications

References 83 publications

Synthesis of Palladium(II) Complexes via Michael Addition: Antiproliferative Effects through ROS-Mediated Mitochondrial Apoptosis and Docking with SARS-CoV-2

Synthesis of Palladium(II) Complexes via Michael Addition: Antiproliferative Effects through ROS-Mediated Mitochondrial Apoptosis and Docking with SARS-CoV-2

Tris-(2-pyridyl)-pyrazolyl Borate Zinc(II) Complexes: Synthesis, DNA/Protein Binding and In Vitro Cytotoxicity Studies

Photochemical and Photobiological Properties of Pyridyl-pyrazol(in)e-Based Ruthenium(II) Complexes with Sub-micromolar Cytotoxicity for Phototherapy

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