Abstract:
Concerns on increasing trends of multidrug resistance (MDR) around the world have triggered the need to investigate and develop new potent antibacterial drugs. Previously Food and Drug Administration (FDA) approved drugs have slowly been outsmarted by bacteria. Hence, 20 Schiff bases and their copper(II) complexes were synthesised and tested in hope to combat MDR. Schiff bases and their copper(II) complexes analogues were characterised by elemental analysis and Fourier-transform infrared spectroscopy (FTIR). The compounds were screened against eight Gram-negative and Gram-positive bacteria: (Acinetobacter baumannii ATCC 19606, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 35923, Acinetobacter baumanni BAA-1797, Escherichia coli BAA-196, Pseudomonas aeruginosa BAA-2108 and Methicillin-resistant Staphylococcus aureus MRSA 43300) to evaluate their antibacterial properties potential based on microbroth dilution. Minimum inhibitory concentration (MIC) results showed the compounds - Cu(SB4CB)2, Cu(SBFH)2, Cu(SBCH)2, Cu(phen)SBFH and Cu(bpy)SBFH have antibacterial potential with MIC values <16 μM indicating good antibacterial potential when tested against susceptible S. aureus ATCC 35923. Among the promising compounds, Cu(SBFH)2 due to its broad spectrum of antibacterial activity was specifically selected for further testing in combination tests alongside membrane permeabilising agent polymyxin B sulfate (POLY) and phenylalanine-arginine-β-naphthylamide (PAβN) against all bacteria. Fractional inhibitory concentration (FIC) index showed improved MIC values with additivity effect for Cu(SBFH)2 in combination with POLY and PAβN. Molecular docking studies had been carried out and demonstrated that Cu(SBFH)2 bound to the active binding site of NorA of S. aureus through hydrogen bonding and pi-pi stacking with Phe140 and hydrophobic interactions with Gly114.
Keywords: Schiff bases, metal complexes, antibacterial, molecular docking, multidrug resistance.
