title: Silver(I) complexes with phthalazine and quinazoline as effective agents against pathogenic Pseudomonas aeruginosa strains.
abstract: Five silver(I) complexes with aromatic nitrogen-containing heterocycles, phthalazine (phtz) and quinazoline (qz), were synthesized, characterized and analyzed by single-crystal X-ray diffraction analysis. Although different AgX salts reacted with phtz, only dinuclear silver(I) complexes of the general formula {[Ag(X-O)(phtz-N)]2(μ-phtz-N,N')2} were formed, X=NO3(-) (1), CF3SO3(-) (2) and ClO4(-) (3). However, reactions of qz with an equimolar amount of AgCF3SO3 and AgBF4 resulted in the formation of polynuclear complexes, {[Ag(CF3SO3-O)(qz-N)]2}n (4) and {[Ag(qz-N)][BF4]}n (5). Complexes 1-5 were evaluated by in vitro antimicrobial studies against a panel of microbial strains that lead to many skin and soft tissue, respiratory, wound and nosocomial infections. The obtained results indicate that all tested silver(I) complexes have good antibacterial activity with MIC (minimum inhibitory concentration) values in the range from 2.9 to 48.0μM against the investigated strains. Among the investigated strains, these complexes were particularly efficient against pathogenic Pseudomonas aeruginosa (MIC=2.9-29μM) and had a marked ability to disrupt clinically relevant biofilms of strains with high inherent resistance to antibiotics. On the other hand, their activity against the fungus Candida albicans was moderate. In order to determine the therapeutic potential of silver(I) complexes 1-5, their antiproliferative effect on the human lung fibroblastic cell line MRC5, has been also evaluated. The binding of complexes 1-5 to the genomic DNA of P. aeruginosa was demonstrated by gel electrophoresis techniques and well supported by molecular docking into the DNA minor groove. All investigated complexes showed an improved cytotoxicity profile in comparison to the clinically used AgNO3.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovića 12, PO Box 60, 34000 Kragujevac, Serbia.
authors.forename: Biljana Đ
authors.initials: BĐ
authors.lastname: Glišić
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Serbia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Senerovic
authors.affiliation: Anorganisch-Chemisches Institüt and Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany. Electronic address: peter.comba@aci.uni-heidelberg.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Comba
authors.affiliation: Anorganisch-Chemisches Institüt and Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Wadepohl
authors.affiliation: Faculty of Medicine, Department of Chemistry, University of Niš, 18000 Niš, Serbia.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Veselinovic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Serbia.
authors.forename: Dusan R
authors.initials: DR
authors.lastname: Milivojevic
authors.affiliation: Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovića 12, PO Box 60, 34000 Kragujevac, Serbia. Electronic address: djuran@kg.ac.rs.
authors.forename: Miloš I
authors.initials: MI
authors.lastname: Djuran
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Serbia. Electronic address: jasmina.nikodinovic@gmail.com.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Nikodinovic-Runic
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms; D018360:Crystallography, X-Ray; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010793:Phthalazines / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D011799:Quinazolines / Q000737:chemistry*; D012834:Silver / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D010793:Phthalazines; D011799:Quinazolines; D012834:Silver; C043388:phthalazine
keywords: Antibacterial activity; Biofilm; Pseudomonas aeruginosa; Silver(I) complexes; Structural characterization