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Half-sandwich Ru(η 6 -p-cymene) complexes featuring pyrazole appended ligands: Synthesis, DNA binding and in vitro cytotoxicity.
- Source :
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Journal of inorganic biochemistry [J Inorg Biochem] 2019 May; Vol. 194, pp. 74-84. Date of Electronic Publication: 2019 Feb 23. - Publication Year :
- 2019
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Abstract
- Organometallic Ru(II)-arene complexes have emerged as potential alternatives to platinum appended agents due to their wide range of interesting features such as stability in solution and solid, significant activity, less toxicity and hydrophobic property of arene moiety, etc. Hence, a series of Ru(II)-p-cymene complexes, [(η <superscript>6</superscript> -p-cymene)Ru(η <superscript>2</superscript> -N,N-L1)Cl]Cl (1), [(η <superscript>6</superscript> -p-cymene)Ru(η <superscript>1</superscript> -N-L2)Cl <subscript>2</subscript> ] (2) and [(η <superscript>6</superscript> -p-cymene)Ru(η <superscript>1</superscript> -N-L3)Cl <subscript>2</subscript> ] (3) were prepared from pyrazole based ligands [2-(1H-pyrazol-3-yl)pyridine (L1), 3-(furan-2-yl)-1H-pyrazole (L2) and 3-(thiophen-2-yl)-1H-pyrazole (L3)], and [RuCl <subscript>2</subscript> -(η <superscript>6</superscript> -p-cymene)] dimer. The new Ru(II)-p-cymene complexes were well characterized by elemental analysis, and spectroscopic (FT-IR, UV-Visible, <superscript>1</superscript> H NMR, <superscript>13</superscript> C NMR and mass) and crystallographic methods. The Ru(II)-p-cymene complexes (1-3) were found to adopt their characteristic piano stool geometry around Ru(II) ion. The calf thymus DNA (CT-DNA) binding ability of the new complexes was investigated by electronic absorption spectroscopic titration and viscosity methods. The molecular docking study results showed that complex 1 strongly bound with targeted biomolecules than 2 and 3. Docked poses of bidentate pyrazole based Ru(II)-p-cymene complex 1 revealed that the complex formed a crucial guanine N <superscript>7</superscript> position hydrogen bond with DNA receptor. Complexes 1-3 might hydrolyze under physiological conditions and form aqua complexes 4-8, and docking calculations showed that the aqua complexes bound strongly with the receptors than original complexes. The in vitro cytotoxicity of the Ru(II)-p-cymene complexes and cisplatin was evaluated against triple negative breast cancer (TNBC) MDA-MB-231 cells. Our results showed that the inhibitory effect of bidentate pyrazole based Ru(II)-p-cymene complex 1 on the growth of breast cancer cells was superior to other tested complexes.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents chemical synthesis
Antineoplastic Agents metabolism
Cattle
Cell Line, Tumor
Cell Survival drug effects
Coordination Complexes chemical synthesis
Coordination Complexes metabolism
Cymenes chemistry
DNA chemistry
Guanine chemistry
Humans
Intercalating Agents chemical synthesis
Intercalating Agents metabolism
Intercalating Agents pharmacology
Ligands
Molecular Docking Simulation
Molecular Structure
Pyrazoles chemical synthesis
Pyrazoles metabolism
Ruthenium chemistry
Antineoplastic Agents pharmacology
Coordination Complexes pharmacology
DNA metabolism
Pyrazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3344
- Volume :
- 194
- Database :
- MEDLINE
- Journal :
- Journal of inorganic biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30831392
- Full Text :
- https://doi.org/10.1016/j.jinorgbio.2019.02.012