New binuclear Ni(II) metallates containing ONS chelators: synthesis, characterisation, DNA binding, DNA cleavage, protein binding, antioxidant activity, antimicrobial and in vitro cytotoxicity

Four new complexes with bridged bis(diphenylphosphino)ethane containing 3-methoxy salicylaldehyde 4(N)-substituted thiosemicarbazone were prepared and characterised by various spectral and analytical techniques. The new complexes were subjected to study their DNA binding, DNA cleavage, protein binding, antibacterial, antioxidant and cytotoxicity. Distorted square planar geometries of complexes 1 and 4 were evidenced from their crystal structures. The complexes could act as strong binders to CT-DNA and BSA. Furthermore, they cleaved supercoiled DNA pBR322. Good spectra of antibacterial activity against five pathogenic bacteria, namely B. Subtilis, S. Aureus, E. Coli, S. Typhi and S. Aurogenosa, were exhibited by the complexes. All the complexes exhibited good antioxidant activity, which was found to be greater than the conventional standard vitamin C. The complexes showed significantly higher cytotoxicity against human cervical cancer cells (HeLa) and human breast cancer cells (MCF-7) than the standard cisplatin. Furthermore, their non-toxic nature was confirmed when they were tested against human normal keratinocyte cells (HaCaT). The compounds induced ROS (Reactive Oxygen Species)-mediated apoptosis, as indicated by DCFDA (2',7'-dichlorodihydro-fluorescein diacetate) and FACS (Fluorescence Activated Cell Sorting) analyses. The complexes showed remarkable values of <3.4 mu M in MCF-7 and <8.4 mu M in HeLa as compared with 23 mu M for cisplatin with both cell lines.