Multi-target activity of copper complexes: Antibacterial, DNA binding, and molecular docking with SARS-CoV-2 receptor. (1st March 2023)

• Record Type: Journal Article
• Authors: Arthi, Padmanathan; Dharmasivam, Mahendiran; Kaya, Busra; Rahiman, Aziz Kalilur
• Is Part Of: Chemico-biological interactions. Volume 373(2023)
• Publication Date: 2023-03-01
• Subjects: Mixed-ligand complexes -- Antibacterial -- DNA interactions -- SARS-CoV-2; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2023.110349
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: A series of pendant-armed mixed-ligand copper(II) complexes of the type [CuL 1-3 (diimine)] (1 –6 ) have been synthesized by the reaction of pendant-armed ligands N, N -bis(2-(((E)-2-hydroxy-5-methylbenzylidene)amino)ethyl)benzamide (H2 L 1 ), N, N -bis(2-(((E)-2-hydroxy-5-methylbenzylidene)amino)ethyl)-4-nitrobenzamide (H2 L 2 ) and N, N -bis(2-(((E)-2-hydroxy-5-methylbenzylidene)amino)ethyl)-3, 5-dinitrobenzamide (H2 L 3 ) with diimine = 2, 2′-bipyridyl (bpy) or 1, 10-phenanthroline (phen) in the presence of copper(II) chloride and analyzed using various spectroscopic methods. All the spectroscopic results support that the complexes adopt a pentagonal-bipyramidal shape around the copper ion. Gram-positive and Gram-negative bacteria were used to test all the complexes for antibacterial activity and all the complexes had greater potency against gram-negative pathogens. DNA-binding experiments of complexes with calf thymus DNA revealed a major-groove binding pattern, further supported by molecular docking studies. Complexes have significantly interacted with SARS-CoV-2 receptor via π-π, π-σ, π-alkyl, π-anion, π-cation, alkyl, hydrogen bond, van der Waals, and electrostatic interactions. The estimated binding energy and inhibition constant of these complexes are higher than standard drugs, chloroquine, and molnupiravir. Graphical abstract: The mechanistic pathways of pendant-armed mixed-ligand copper(II) complexes remarkably damage DNA, and protein and increase the ROS followed by electron transfer reactions. Image 1 Highlights: New Cu(II) complexes exhibit pentagonal bipyramidal geometry. The complexes showed high potency against Gram-negative pathogens. Mixed-ligand Cu(II) complexes bind to DNA via the major groove region. Higher binding potency against the SARS-CoV-2 receptor relative to standard drugs.