Open Chemistry (Dec 2020)
Antimicrobial and antifungal activities of bifunctional cooper(ii) complexes with non-steroidal anti-inflammatory drugs, flufenamic, mefenamic and tolfenamic acids and 1,10-phenanthroline
Abstract
Cooper(ii) complexes represent a promising group of compounds with antimicrobial and antifungal properties. In the present work, a series of Cu(ii) complexes containing the non-steroidal anti-inflammatory drugs, tolfenamic acid, mefenamic acid and flufenamic acid as their redox-cycling functionalities, and 1,10-phenanthroline as an intercalating component, has been studied. The antibacterial activities of all three complexes, [Cu(tolf-O,O′)2(phen)] (1), [Cu(mef-O,O′)2(phen)] (2) and [Cu(fluf-O,O′)2(phen)] (3), were tested against the prokaryotic model organisms Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) and their antifungal activities were evaluated towards the yeast, Saccharomyces cerevisiae (S. cerevisiae). The antibacterial activity of both strains has been compared with the antibiotic Neomycin. The calculated IC50 values revealed slight differences in the antibacterial activities of the complexes in the order 1 ∼ 3 > 2. The most profound growth inhibition of E. coli was observed, at its highest concentration, for the complex 1, which contains chlorine atoms in the ligand environment. The trend obtained from IC50 values is generally in agreement with the determined MIC values. Similarly, the complex 1 showed the greatest growth inhibition of the yeast S. cerevisiae and the overall antifungal activities of the Cu(ii) complexes were found to follow the order 1 > 3 ≫ 2. However, for complex 2, even at the highest concentration tested (150 μM), a 50% decrease in yeast growth was not achieved. It appears that the most potent antimicrobial and antifungal Cu(ii) complexes are those containing halogenated NSAIDs. The mechanisms by which Cu(ii) complexes cause antibacterial and antifungal activities can be understood on the basis of redox-cycling reactions between cupric and cuprous species which lead to the formation of free radicals. The higher efficacy of the Cu(ii) complexes against bacterial cells may be due to an absence of membrane-protected nuclear DNA, meaning that on entering a cell, they can interact directly with its DNA. Contrastingly, for the complexes to interact with the DNA in yeast cells, they must first penetrate through the nuclear membrane.
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