Developing effective copper(II) based antimicrobial agents

Abstract

Antimicrobial drug resistance is increasing at an alarming rate while the availability of new and effective antibiotics for treating microbial infections is reducing and will eventually be exhausted. It is estimated that by the year 2050, the death rates will increase to about 10 million people a year due to antimicrobial resistance and the Gross Domestic Product of countries will be reduced by 2-3.5%. In efforts attempt to address this problem, copper(II) complexes with a structural formula of [Cu(PL)2(H2O)n]2+ (where n = 0 or 1) or [Cu(N4-TL)(H2O)]2+ new complexes include: PL = derivatives of 1,10-phenanthroline and 2,2'-bipyridine, N4-TL = N,N-bis(2-pyridyl)-1,2-diiminoethane (picen) and its derivatives, were synthesised and their antibacterial activity investigated against Gram-positive bacteria Staphylococcus aureus, Gram-negative bacteria Pseudomonas aeruginosa, Escherichia coli and yeast Candida krusei, were determined. Characterisation was accomplished using techniques such as UV-Vis spectroscopy, electrospray ionisation mass spectroscopy (ESI-MS), X-ray crystallography and elemental analysis. Antimicrobial activities of the synthesised species were determined using Minimum Inhibitory Concentration (MIC90) and anti-biofilm assay. Complexes based on derivatives of phenanthroline and bipyridine ligands demonstrated significant activity against S. aureus. [Cu(29Me2phen)] was demonstrated to be the most active against S. aureus, E. coli and C. krusei at considerably low concentrations with a starting concentration of 4 µM. N4-Tetradentates based copper complexes exhibited no significant activity against any microbial species. Preliminary anti-biofilm studies were performed on S. aureus biofilms against Cu1, Cu4 and Cu7, with ampicillin as control. Cu4 demonstrated maximum eradication as compared to Cu1, Cu7 and ampicillin at concentration of 59 µM, whereas ampicillin eradicated only 5% biomass at 91 µM.

Date of Award	2017
Original language	English