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Copper (II) complexes based bis(pyrazolyl)borate derivatives as efficient anticancer agents: synthesis, characterization, X-ray structure, cytotoxicity, molecular docking and QSAR studies

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Abstract

Copper-based complexes have various applications in the current era, particularly in the field of pharmaceutical and biochemistry. Four types of the bis(pyrazolyl) borate-based ligands that abbreviated K[H2B(Pz)2] (1), K[H2B(PzMe2)2] (2), K[H2B(PzMe3)2] (3), K[H2B(PzPhMe)2] (4) and their Cu(II) complexes (5–8) were synthesized and characterized by spectroscopic and analytical tools. An ideal square planar structure of complex (6) was confirmed by single-crystal X-ray crystallography. The anticancer potential of synthesized ligands and complexes was investigated using MTT assay against MCF-7 cell lines, and among the investigated compounds, complex [Cu(H2B(Pz)2)2] (5) showed the lowest IC50 values. Molecular docking studies indicated that copper complexes indicate a better binding energy in comparison with free ligands. Complex [Cu(H2B(PzMe2)2)2] (6) that bound to CDK2 protein and the ligand K[H2B(PzPhMe)2] (4) that bound to EGFR protein have the highest binding energy among the investigated compounds. In addition, quantitative structure–activity relationship (QSAR) studies indicated that EHOMO and dipole moment is in direct correlation with the obtained IC50 values and strongly effect on the anticancer cytotoxicity response.

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Acknowledgements

We are grateful to the University of Azarbaijan Shahid Madani for supporting this research. The cytotoxicity assay of the compounds was performed in Faculty of Medicine of Tabriz University of Medical Sciences. Single-crystal X-ray crystallography experiments were performed at the University of Akron. The optimization of the structure of the compounds was performed in the Molecular Simulation laboratory of Azarbaijan Shahid Madani University. Also we are so grateful to Prof. Dr Jaber Jahanbin Sardroodi, Dr. Rahim Mohammad-Rezaei and Dr. Ali Mota for their helpful collaboration.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Basic Science, Azarbaijan Shahid Madani University, P.O.Box 53714-161, Tabriz, Iran

    Monireh Ghorbanpour & Behzad Soltani

  2. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

    Ommoleila Molavi & Elnaz Mehdizadeh Aghdam

  3. Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Ali Shayanfar

  4. Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran

    Elnaz Mehdizadeh Aghdam

  5. Department of Chemistry, University of Akron, Akron, Ohio44325, USA

    Christopher John Ziegler

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  1. Monireh Ghorbanpour
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Correspondence to Behzad Soltani.

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11696_2022_2288_MOESM1_ESM.docx

Supplementary file1 (DOCX 15 KB) CCDC 2061346 contains the supplementary crystallographic data for 6. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif

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Ghorbanpour, M., Soltani, B., Molavi, O. et al. Copper (II) complexes based bis(pyrazolyl)borate derivatives as efficient anticancer agents: synthesis, characterization, X-ray structure, cytotoxicity, molecular docking and QSAR studies. Chem. Pap. 76, 7343–7356 (2022). https://doi.org/10.1007/s11696-022-02288-9

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