title: Inhibition of the hemolytic activity caused by Staphylococcus aureus alpha-hemolysin through isatin-Schiff copper(II) complexes.
abstract: A great number of pathogens secrete pore-forming proteins during infection. Such molecules, from either bacterial or viral origin, are considered important virulence factors, which makes them attractive targets in the study of new therapeutic agents. Thus, the inhibitory activity of isatin-Schiff base copper(II) complexes was evaluated against membrane damage activity of Staphylococcus aureus α-hemolysin (α-HL). For this purpose, a standard hemolysis assay with rabbit erythrocytes and micromolar concentrations of the compounds was employed. Additionally, planar artificial lipid membranes with a single α-HL ion channel and molecular docking studies were used to elucidate the molecular mechanism of the complexes. Accordingly, the compounds were observed to possess a significant anti-hemolytic activity, capable of interacting with the constriction region of α-HL channel and blocking it in a potential dependent manner. Based on these results, it is expected that such isatin-Schiff base Copper(II) complexes may be employed as cotherapeutic agents for the treatment of staphylococcal infections.
authors.affiliation: Laboratory of Membrane Biophysics and Stem Cell Dr. Oleg Krasilnikov, Department of Biophysics and Radiobiology, Federal University of Pernambuco, Recife, Pernambuco, Brazil.
authors.forename: Maria C A
authors.initials: MC
authors.lastname: Melo
authors.affiliation: Laboratory of Membrane Biophysics and Stem Cell Dr. Oleg Krasilnikov, Department of Biophysics and Radiobiology, Federal University of Pernambuco, Recife, Pernambuco, Brazil.
authors.forename: Luciana R
authors.initials: LR
authors.lastname: Teixeira
authors.affiliation: Biomaterials Laboratory, Department of Fundamental Chemistry, Federal University of Pernambuco, Recife, Pernambuco, Brazil Aggeu Magalhães Research Center, Oswaldo Cruz Foundation, Recife, Pernambuco, Brazil.
authors.forename: Laercio
authors.initials: L
authors.lastname: Pol-Fachin
authors.affiliation: Laboratory of Membrane Biophysics and Stem Cell Dr. Oleg Krasilnikov, Department of Biophysics and Radiobiology, Federal University of Pernambuco, Recife, Pernambuco, Brazil cgrufpe@gmail.com.
authors.forename: Claudio G
authors.initials: CG
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D000992:Antitoxins / Q000737:chemistry / Q000378:metabolism*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects*; D006460:Hemolysin Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006461:Hemolysis; D007510:Isatin / Q000737:chemistry / Q000378:metabolism*; D062105:Molecular Docking Simulation; D011817:Rabbits; D012545:Schiff Bases / Q000737:chemistry / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism*
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D012545:Schiff Bases; C021091:staphylococcal alpha-toxin; D003300:Copper; D007510:Isatin
keywords: Staphylococcus aureus; antibacterial; copper(II) complexes; ion channel; isatin-Schiff; α-hemolysin