ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

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

Monireh Ghorbanpour, Behzad Soltani, Ommoleila Molavi, Ali Shayanfar, Elnaz Mehdizadeh Aghdam, and Christopher John Ziegler

Department of Chemistry, Faculty of Basic Science, Azarbaijan Shahid Madani University, Tabriz, Iran

E-mail: bh_soltani@yahoo.com

Received: 4 January 2022  Accepted: 18 May 2022

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(Pz^Me2)₂] (2), K[H₂B(Pz^Me3)₂] (3), K[H₂B(Pz^PhMe)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(Pz^Me2)₂)₂] (6) that bound to CDK2 protein and the ligand K[H₂B(Pz^PhMe)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 E_HOMO and dipole moment is in direct correlation with the obtained IC₅₀ values and strongly effect on the anticancer cytotoxicity response.

Graphical Abstract

Keywords: Bis(pyrazolyl)borate derivatives; Cu (II) complexes; Crystal structure; Anti-cancer activity; Molecular docking; QSAR

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-022-02288-9

Chemical Papers 76 (12) 7343–7356 (2022)