Synthesis, characterization, computational studies and biological activity evaluation of Cu, Fe, Co and Zn complexes with 2-butanone thiosemicarbazone and 1,10-phenanthroline ligands as anticancer and antibacterial agents.

Mixed-ligand metal (II) (M=Cu, Fe, Co and Zn) complexes containing 2-butanone thiosemicarbazone and 1, 10-phenanthroline have been synthesized and characterized by melting point, FT-IR, 1 H-NMR, UV-spectrophotometry and molar conductance measurements. All the complexes were soluble in DMSO and DMF. They were thermally stable with high melting points. The computational studies of the complexes were also performed to assess toxicity potential, bioactivity score prediction and drug likeliness assessment based on various drug filters. All the complexes showed no Veber's violations whereas only Cu complex showed one Lipinski's violation. Almost all synthesized compounds were predicted to have no toxic effects. Some of them showed positive bioactivity as enzyme inhibitors. Molecular docking of the complexes was also performed against ribonucleotide diphosphate reductase (RR) and topoisomerase II (Topo II) for minimum binding energy (kcal/mol) calculations. Cu complex was found to have minimum binding energy (-101.13 kcal/mol) released on interaction with Topo II showing a high affinity towards the enzyme, whereas Fe complex had the lowest binding energy (-99.8349 kcal/mol) when docked with RR. The results were compared with two standard drugs i.e. doxorubicin HCl and tetracycline. The ligand was tested for its potential anticancer activity against MDA-MB-231 cell line using MTT assay. Antibacterial activity of the complexes was tested against Staphylococcus aureus and Escherichia coli using the disc diffusion method. Cu (II) complex showed maximum activity against the MDA cells and also exhibited mild antibacterial activity against S. aureus .