Copper (II) complexes with N, S donor pyrazole-based ligands as anticancer agents

A group of bidentate nitrogen and sulfur donor pyrazole derivative ligands abbreviated as Na[RNCS(Pz)], Na[RNCS(Pz Me2 )], Na[RNCS(Pz Me3 )], Na[RNCS(Pz PhMe )], Na[RNCS(Pz Ph2 )], where (R = Et, Ph), and their Cu (II) complexes were synthesized and characterized by spectroscopic and physicochemical methods. The crystal structure of [Cu(PhNCSPz Me3 ) 2 ] was determined by X-ray crystallography analysis and the results described a distorted square planar coordination geometry for this complex. Also, the cyclic voltammetry investigations indicated that the synthesized copper complex is an electrochemically active species. Moreover, the cytotoxic activity of all of the twenty synthesized compounds was evaluated using MTT assay against the MCF-7 (human breast carcinoma) cell lines, in vitro. Cu (II) complexes indicate significant cytotoxicity against the MCF-7 cell lines as compared with the free ligands. The docking studies showed that the copper complexes have better interactions with EGFR and CDK2 proteins, compared to the free ligands, and most of the studied compounds have a higher value of binding energy relative to the studied controls. The results of QSAR analysis suggest that dipole moment is in direct correlation with the obtained IC 50 values, and it strongly impact the anticancer effects generated by the compounds. Our findings suggest that the developed copper complexes can be good candidates for further evaluations as chemotherapeutic agents in the treatment of cancer. Graphical abstract