Experimental and Computational Insights of Schiff Base Copper(II) Complexes of Para-Substituted Benzaldehydes towards some Bacterial and Target Proteins

Abstract

The search for new antibacterials via in-vitro and computational techniques that support green and sustainable technologies for use in the future necessitated this study, as molecular docking has proved to be a promising lead in development of target drugs. Herein, we report novel copper (II) complexes F1Cu-F3Cu with Schiff bases synthesized from para-substituted benzaldehydes and ortho-aminophenol. The compounds were characterized using elemental analysis, atomic absorption spectroscopy, infrared spectroscopy, ¹H NMR, and electronic absorption spectroscopy. In-vitro antibacterial study against 6 human pathogenic bacteria; Escheriachia coli (ATCC 8739), Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 19582), Bacillus cereus (10702), Enterococcus faecalis (ATCC 29212) and Kribsella pneumonia (ATCC 10031) revealed an increase in antibacterial activity with the copper complexes against the free ligands. This was compared with ampicillin as a reference. To further confirm the activity of the complexes, molecular docking was employed against some clinically important bacterial target proteins specific to each bacterium, which revealed a strong correlation with the experimental antibacterial activity (MIC values) for all the targets studied. The docking results show that the complexes exhibited a much stronger binding interaction with the proteins compared to the parent ligands, with the former having scores of −7.4 to −10.1 kcal/mol and the latter scoring −5.7 to −7.4 kcal/mol. Also, inhibition of the DHFR enzyme by the complexes prevents any substrate from accessing the enzyme, thus disrupting of the folate cycle that is important for the growth of bacteria.  Our synergistic results have shown that these complexes can be developed as an antibacterial agent in drug discovery.