Copper(ii) complexes with aromatic nitrogen-containing heterocycles as effective inhibitors of quorum sensing activity in Pseudomonas aeruginosa

Abstract

Copper(ii) complexes with aromatic nitrogen-containing heterocycles are a new class of quorum sensing inhibitors that attenuate virulence without a pronounced effect on the bacterial growth, thus offering a lower risk for resistance development.

Synthesis, Structural Characterization and Antimicrobial Evaluation of Ruthenium Complexes with Heteroaromatic Carboxylic Acids

“…The high activity was detected for the compound 1 against bacterium of P. aeruginosa PAO1 with the MIC value 0.5 m m (302 μg/ml). Considering the MIC values for other transition metal complexes towards P. aeruginosa PAO1 (Ag(I) complexes – MIC=2–15 μg/ml, Au(III) complexes – MIC=10−30 μg/ml, Cu(II) complexes – MIC=500–1000 μg/ml), it can be concluded that the tested ruthenium complexes show moderate bacteriostatic activity. In comparison to tested antibiotic, the studied ruthenium compounds exhibit much lower bacteriostatic effects on the bacteria.…”

“…Biologically active metal complexes have gained special significance due to the need for the prevention of resistance of bacterial strains. Recently, several Cu(II), Ga(III), Zn(II), Mn(II), Ag(I), Au(III) and Ru(II) complexes with bioactive ligands have been tested as potential antibiofilm and antimicrobial agents . Among above mentioned metal complexes, ruthenium compounds are promising for medicinal and biotechnological applications as they present unique properties: (i) multiple oxidation states (II, III and IV), which are accessible in physiological conditions; (ii) favorable ligand‐exchange kinetics; (iii) multiple cytotoxic routes involving the competing processes of extracellular protein binding (active transport), due to the ability to mimic iron and cellular uptake (passive diffusion); (iv) different molecular pathways involving the concurrent intercalation and covalent binding with DNA and binding to extracellular sites inducing conformational modifications; (v) numerous synthetic opportunities for modifying the biological activity which depends on both the oxidation state of the metal center and the associated ligands surrounding it.…”

Different coordination abilities of 1,7- and 4,7-phenanthroline in the reactions with copper(II) salts: Structural characterization and biological evaluation of the reaction products

“…Copper(II) complexes with 4,7-phenanthroline, [Cu(NO 3 ) 2 (4,7-Hphen) 2 ](NO 3 ) 2 (1) and [Cu(CF 3 SO 3 )(4,7-phen) 2 (H 2 O) 2 ]CF 3 SO 3 (2) were synthesized according to the modified procedure for the preparation of copper(II) complexes with aromatic N-heterocycles [22]. The solution of 0.5 mmol of CuX 2 salt (120.8 mg of Cu(NO 3 ) 2 -Á3H 2 O for 1 and 180.8 mg of Cu(CF 3 SO 3 ) 2 for 2) in 5.0 mL of ethanol was added slowly under stirring to the solution containing an equimolar amount of 4,7-phen (90.1 mg) in 5.0 mL of ethanol.…”

“…Very recently, five copper(II) complexes with aromatic nitrogen-containing heterocycles (N-heterocycles), e.g. pyrimidine, pyrazine, quinazoline and phthalazine, were synthesized and evaluated for their activity against three clinically important pathogens, namely Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans [22]. The obtained results showed that none of the studied copper(II) complexes manifested significant growth inhibiting activity against the investigated strains.…”

“…The obtained results showed that none of the studied copper(II) complexes manifested significant growth inhibiting activity against the investigated strains. Nevertheless, these complexes were able to inhibit bacterial quorum sensing (QS) through the modulation of the level of signaling molecules that are part of QS system [22]. This finding was very important in view of the development of novel therapeutic agents that attenuate virulence rather than microbial growth, thus offering a lower risk of resistance development.…”