Synthesis of novel Cu(II) complexes with N2O2 ligands: Characterization, theoretical calculations, antimicrobial, antioxidant, DNA binding, and in vitro anticancer activity studies

Abstract

The aim was to investigate the in vitro antimicrobial, antioxidant, cytotoxic activities and pBR322 Plasmid DNA interaction potentials of newly synthesized Schiff bases and their copper complexes. Cytotoxic activities of these compounds were determined by MTT methods in human breast cancer (MCF-7), human cervical cancer (HeLa) and mouse fibroblast (L929) cell lines. The determination of changes in oxidant and antioxidant load of the cell after application of these compounds were investigated with the aid of Rel Assay Diagnostics kits. It was found that the some of the compounds had moderate antimicrobial activity, and oxidative stress index. According to plasmid DNA interaction studies, synthesized complexes modified the tertiary structure of pBR322 plasmid DNA. The compound Bis-Napht showed the highest cytotoxic activity in HeLa, MCF-7 and L929 cells at an IC50 dose of 3 ± 1 μM, 5 ± 1 μM and 3 ± 1 μM respectively. Compound Bis-Sal was determined to have lower cytotoxic activity in L-929 cells at an IC50 dose of 106 ± 9 μM at 24 h compared to other compounds. Ligand compounds and their metal complexes were optimized on the B3LYP, HF, and M06-2x methods with the 6–31++g(d,p) basis set. Afterwards, their activities were compared against crystal structure of the BRCT repeat region from the breast cancer associated protein, (BRCA1) (PDB ID: 1JNX) and crystal Structure of CDK2 receptor of cervical cancer cell proteins (PDB ID: 4BGH). To examine the interactions occurring in more detail, Protein-Ligand Interaction Profiler analysis was performed and all chemical interactions that occurred were determined.