Synthesis, characterization, cytotoxicity evaluation, and molecular docking with DNA, bovine serum albumin, and SARS-Cov-2 of copper complexes bearing tris-(2-pyridyl)-pyrazolyl borate ligand

Four copper (II) complexes bearing tris-(2-pyridyl)-pyrazolyl borate (Tp(py)) ligand with corresponding chloride (Cu-1), aqua (Cu-2), azide (Cu-3), and thiocyanide (Cu-4) substitutions were synthesized and characterized by spectroscopic and analytical methods. Spectroscopic and molecular docking studies were employed to investigate the interactions of these complexes with calf thymus (CT) DNA and bovine serum albumin (BSA). The results inferred intercalation binding mode of the complexes with DNA. All the complexes exhibited good binding with BSA as well. In addition, the binding efficacy of the Cu (II) complexes with SARS-Cov-2 was tested in silico. Further, in vitro anticancer activity of the complexes was investigated against the HeLa-cervical, HepG2-liver and A549-lung cancer, and one normal (L929-fibroblast) cell line. IC50 values unveiled that the complexes were more active than cisplatin against all three cancer cells. It was understood that complex Cu-3 containing azide substitution displayed the highest activity on the HeLa cell line (IC50 = 6.3 mu M). More importantly, Tp(py)Cu (II) complexes were not active against the normal cell line. Lastly, the acridine orange/ethidium bromide (AO/EB) and 4 ',6-diamidino-2-phenylindole staining assays indicated that Cu-3 induced cell death in HeLa cells at the late apoptotic stage. This complex also efficiently generated ROS in HeLa cells promoting apoptosis as understood from the DCFH-DA assay.