Synthesis, characterization, molecular docking and biological activity of 5,6-bis-(4-fluoro-phenyl)-3,4,7,8-tetraaza-bicyclo[8.3.1]tetradeca-1(13),4,6,10(14),11-pentaene-2,9-dione and its transition metal complexes

Macrocyclic Schiff base ligand through the condensation of 1,3-dicarbonyl-phenyl-dihydrazide with 4,4′-difluorobenzil and its Co(II), Ni(II), Cu(II) and Zn(II) metal complexes have been synthesized. The ligand and metal complexes were characterized by analytical and physicochemical methods. An octahedral geometry arising from coordination of N2O2 donor atoms from the macrocyclic framework has been proposed for all metal complexes. Synthesized ligand and metal complexes were investigated for in vitro antibacterial and antioxidant activity. Complex [Ni(C22H14N4F2O2)(OCOCH3)2] has shown remarkable antibacterial activity (Minimum inhibitory concentration 8-16 μg/ml) comparable to commercial antibiotic Ciprofloxacin. Anticancer activity of synthesized compounds against Squamous Cell Carcinoma (SCC4), head and neck cancer cell line has also been studied at different concentrations and at different time points. Complexes [Co(C22H14N4F2O2)(NO3)2] and [Cu(C22H14N4F2O2)(OCOCH3)2] have shown remarkable anticancer results (IC50 31.1 and 43.1 μM) against the tested cell line in concentration dependent manner. Molecular docking studies were carried out to find the binding mode of the synthesized macrocyclic Schiff base ligand to Epidermal Growth Factor Receptor (EGFR) Kinase (PDB ID: 1M17).