Transition metal complexes of pyridazine-based ligand: synthesis, characterization, biological activities, and molecular docking studies

A new class of pyridazine-based six Iron(II), Nickel(II) and Copper(II) metal complexes of (E)-2-(6-chloropyridazin-3-yl)-1-(1-(pyridin-2-yl)ethylidene)hydrazine ligand (L1)(1) derived from condensation of 2-(6-chloropyridazin-3-yl)hydrazine and pyridine-2-acetaldehyde were synthesized in 1:1 and 1:2 molar ratio with ligand and characterized by UV-visible, 1H- and 13C-NMR, FT-IR, mass and EPR spectroscopy, elemental analysis and molar conductance. The spectroscopic evidence specifies that the ligands behave as a tridentate ligand through the nitrogen atom of pyridine-2-acetaldehyde, nitrogen atoms of azomethine group and pyridazine ring. The mass spectra demonstrated that the complexes have prepared in 1:1 and 1:2 molar ratio with ligand and suitable metals salts. From the ESR spectroscopy, confirmed that the Cu(L1)(4) complex had the square planar geometry, whereas Cu(L1)2(7) complex had distorted octahedral geometry. The ligand and its six metal complexes were evaluated for their in vitro antibacterial activity against Staphylococcus aureus (MTCC 96), Streptococcus pyogenes (MTCC 442), Escherichia coli(MTCC 443), Pseudomonas aeruginosa (MTCC 1688) strains, and in vitro antifungal activity against Candida albicans (MTCC 227), Aspergillus niger (MTCC 282), and Aspergillus clavatus (MTCC 1323) strains by using micro-broth dilution method against standard antibiotics Gentamycin, Ampicillin, Chloramphenicol, Ciprofloxacin, Norfloxacin, and antifungal agents Nystatin and Griseofulvin. Cytotoxicity assays against human colon cancer MiaPaCa-2 and PanC-1 cell lines in vitro were completed for ligand (L1) by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium by (MTT) method. Finally, the optimized structures of the ligand and its complexes have been used to accomplish molecular docking studies with receptors of DNA Gyrase (PDB ID-1aj6) enzyme to determine the most preferred mode of interaction.