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The anticancer impacts of N, S donor pyrazole based ligand and its Co(III) and Cu(II) complexes on breast cancer cells

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Abstract

The development of suitable compounds for the effective treatment of cancer is highly demanded. Inorganic complexes based on cobalt and copper centers have revealed a great potential for the treatment of various cancers. The current study aimed to develop effective pyrazole-based agents against breast cancer. A pyrazole-based ligand (L: Na[EtNCSPzMe2]) and its cobalt and copper complexes were synthesized, and the single crystals of the complexes were prepared for crystallographic analysis. The X-ray structure of the synthesized complexes indicated both of the complexes were mononuclear and monoclinic. The synthesized [Co(L)3] complex demonstrated a six-coordinated distorted octahedral geometry around the cobalt center, while the [Cu(L)2] complex occupied a four-coordinated seesaw geometry with N2S2 environment around the copper center. The compounds were evaluated for their anticancer activities against the human breast MDA-MB-231 cell lines with the MTT and flow cytometry assays to investigate the efficacy of these synthesized compounds in the induction of apoptosis and death in breast cancer cells. The investigated complexes significantly indicated more anticancer activity in compare with the free ligand and the among them Cu(II) complex showed considerable and higher activity against the tested cell lines. The molecular docking was carried out to explore the binding modes of these compounds on DNA and epidermal growth factor receptor precursor (EGFR) proteins. Altogether, in silico and in vitro investigations indicated that coordination of chelating organic ligand to the metal centers promoted the compounds anticancer activity and these complexes may be used the likely candidate for further development in cancer treatment after complementary preclinical evaluations.

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Data availability

The data that support the findings of this study are available on request from the corresponding author.

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Acknowledgements

We are grateful to the University of Azarbaijan Shahid Madani for supporting of this research. The cytotoxicity and flow cytometry assays of the compounds were performed in the Tabriz University of Medical Sciences. Single crystal X-ray diffraction experiments were performed at the University of Akron. We thank them 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. Pharmaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

    Ali Shayanfar

  3. Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Ali Mota & Abbas Pirpour Tazehkand

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

    Elnaz Mehdizadeh Aghdam

  5. Department of Chemistry, University of Akron, Akron, OH, 44325, USA

    Christopher J. Ziegler

Authors
  1. Monireh Ghorbanpour
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  2. Behzad Soltani
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  3. Ali Shayanfar
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  4. Ali Mota
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  5. Elnaz Mehdizadeh Aghdam
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Contributions

Conceptualization was contributed by [BS, AS, MG, AM, EMA], Supervision was contributed by [BS, AS, AM, EMA],Writing—review and editing, was contributed by [BS, AS, MG, AM, EMA, APT], Formal analysis was contributed by [CJZ], Writing—original draft preparation, was contributed by [ BS, AS, MG, AM].

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Correspondence to Behzad Soltani.

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Appendix

Appendix

CCDC 2,159,568 and 2,124,457 contain the supplementary crystallographic data for 1 and 2. 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., Shayanfar, A. et al. The anticancer impacts of N, S donor pyrazole based ligand and its Co(III) and Cu(II) complexes on breast cancer cells. Transit Met Chem 47, 311–320 (2022). https://doi.org/10.1007/s11243-022-00514-7

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