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

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.

Automated summary

Copper-based complexes have diverse applications in pharmaceutical and biochemistry. In this study, four types of bis(pyrazolyl) borate-based ligands and their copper(II) complexes were synthesized and characterized. One of the complexes showed promising anticancer potential and molecular docking studies revealed better binding energy for copper complexes.