Synthesis of thiosemicarbazide-based zinc complexes and evaluation of their inhibition of bacterial biofilm formation via targeting extracellular proteins.

Three new zinc(II) complexes with N-benzyl-2-((2-hydroxynaphthalen-1-yl)methylene) hydrazine-1-carbothioamide-methanol solvate (L), 1,10-phenanthroline (phen), and pyridine (py) as ligands, were synthesized and fully characterized. They are named as [Zn2(L)2Cl2)].CH3OH (1), [Zn(L)(phen)].CH3OH (2), and [Zn2(L)2(py)2] (3). Complex 1 and 3 are dinuclear structures. Complex 1 contains two L ligands; complex 3 also contains two L ligands in addition of two py as co-ligands, and complex 2 is mononuclear with one L and one phen as co-ligand. The in vitro antibacterial activities of complexes 1-3 were tested on five bacterial strains with minimum inhibitory concentrations (MICs) of 1.56 to 64 μg/mL. Complexes 1 and 2 exhibited significantly stronger antibacterial activity against Enterococcus faecalis (E. faecalis) and methicillin-resistant Staphylococcus aureus (MRSA) (S. aureus) than L, complex 3, and Vancomycin. The complexes 1 and 2 inhibited bacterial biofilm formation at concentrations from 0.5 to 10 μg/mL, higher than L, complex 3 and Vancomycin. Complexes 1 and 2 strongly interacted with extracellular proteins (ECPs) of bacterial biofilms. Furthermore, molecular docking (MD) studies have validated the interactions of L and complexes 1-3 with biofilm-associated proteins (Baps) and SARS-CoV-2 receptors, positioning these zinc(II) complexes as promising candidates for developing antibacterial and anti-biofilm agents.