Abstract
AbstractCooper(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.
Highlights
It has been reported that in the USA alone, more than 50,000 patients die annually from multiresistant bacterial infections [1]
We report the antibacterial and antifungal activities of Cu(II) complexes bearing 1,10phenanthroline as an intercalating ligand and the nonsteroidal anti-inflammatory drugs: tolfenamic acid, mefenamic acid and flufenamic acid, to provide redoxcycling functionalities (Figure 1)
All three complexes are monomeric and crystallize in the monoclinic space group, and in each case, the Cu(II) ion is chelated in the equatorial plane by the two 1,10-phenanthroline nitrogen atoms and a total of four carboxylate oxygen atoms from two molecules of the particular NSAID [14]
Summary
It has been reported that in the USA alone, more than 50,000 patients die annually from multiresistant bacterial infections [1]. Antimicrobial and antifungal activities of bifunctional copper(II) complexes 1445 elements in the human body and is a redox active metal, whose positive effects on human health were first noted as early as the late 19th century, when it was reported by Doctor Luton that a mixture of copper chloride and sodium salicylate was effective in the treatment of rheumatoid arthritis, rheumatic fever and other disorders [8] This observation was later augmented during the first half of the 20th century in Finland, where miners who worked in copper mines were found to suffer a considerably lower incidence of arthritis than the majority of population. There is no direct proof that Cu(III) species exist in biological systems, which would require the presence of a redox active cofactor Most common are those complexes containing copper in the +2 oxidation state and these show inhibitory effects toward the growth of a variety of bacteria, fungi and viruses [10,11,12,13]. In addition to this intercalation mechanism, a process of redox cycling, with the formation of DNA damaging ROS, may occur
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