Synthesis, structural characterization and in vitro antibacterial activity studies of ternary metal complexes of anti-inflammatory bromhexine drug

Abstract

A novel d-block metal complexes of M(II)/(III) ions using bromhexine (BHX) as primary ligand and glycine (GLY) as secondary ligand were synthesized and characterized. The structures of these complexes were confirmed by different spectroscopic tools. From the molar conductivity, elemental analyses and thermal analysis data of the synthesized complexes, general formula of [M(BHX)(Gly)(H2O)2]XCl·yH2O, (where M = Cr(III), x = y = 2; Mn(II), Co(II), Ni(II), Cu(II) and Zn(II), x = 1, y = 0; Cd(II), x = 1, y = 2) and [Fe(BHX)(Gly)(H2O)Cl]Cl with an octahedral structure were proposed. The octahedral geometry was supported by the magnetic moment and diffuse solid reflectance spectra measurements. The IR spectra pointed out that BHX ligand coordinated in neutral bidentate mode to the metal ions while Gly coordinated in mono negative bidentate mode. Conductivity measurements revealed that the ternary complexes were electrolytes. The complexes were tested against a variety of pathogenic bacterial strains and shown to have effective antibacterial capabilities when compared to bromhexine, suggesting that they could be useful models for the development of effective antibiotic drug molecules. In addition, the ligands were tested for anticancer activity against the MCF-7 breast cancer cell line, and the results revealed that the metal complexes were more active than the parent BHX free ligand. The BHX ligand and Co(II) complex were molecular docked to a variety of potential biological targets, including the receptors of Staphylococcus aureus crystal structure (PDB ID: 4K3V) and the receptors of breast cancer mutant oxidoreductase (PDB ID: 3HB5).