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. 2023 Mar 1:373:110349.
doi: 10.1016/j.cbi.2023.110349. Epub 2023 Jan 11.

Multi-target activity of copper complexes: Antibacterial, DNA binding, and molecular docking with SARS-CoV-2 receptor

Padmanathan Arthi  1 , Mahendiran Dharmasivam  2 , Busra Kaya  3 , Aziz Kalilur Rahiman  4
Affiliations

Multi-target activity of copper complexes: Antibacterial, DNA binding, and molecular docking with SARS-CoV-2 receptor

Padmanathan Arthi et al. Chem Biol Interact. .

Abstract

A series of pendant-armed mixed-ligand copper(II) complexes of the type [CuL1-3(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 (H2L1), N,N-bis(2-(((E)-2-hydroxy-5-methylbenzylidene)amino)ethyl)-4-nitrobenzamide (H2L2) and N,N-bis(2-(((E)-2-hydroxy-5-methylbenzylidene)amino)ethyl)-3,5-dinitrobenzamide (H2L3) 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.

Keywords: Antibacterial; DNA interactions; Mixed-ligand complexes; SARS-CoV-2.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Scheme 1
Scheme 1
Synthesis of pendant-armed mixed-ligand copper(II) complexes (1–6).
Fig. 1
Fig. 1
(A) 1H NMR and (B) 13C NMR spectra of the ligand H2L2.
Fig. 2
Fig. 2
ESI-MS spectrum of the ligand H2L1.
Fig. 3
Fig. 3
ESI-MS spectrum of the complex 1.
Fig. 4
Fig. 4
UV–Vis spectra of pendant-armed mixed-ligand copper(II) complexes (1–6); insert d–d band of the complexes.
Fig. 5
Fig. 5
Optimized molecular structures of pendant-armed copper(II) complexes (1–6) (A–F).
Fig. 6
Fig. 6
Antibacterial activity of complexes (1–6) against Gram (-ve) and Gram (+ve) bacteria.
Fig. 7
Fig. 7
Potential mechanistic pathways of copper(II) complexes (1–6).
Fig. 8
Fig. 8
Absorption spectra of the pendant-armed polyaza mixed-ligand mononuclear copper(II) complex 1 (A) and 2 (B) (10 μM) in Tris-HCl/NaCl (pH 7.2) buffer upon addition of CT–DNA (0–100 μM). The arrow shows the absorbance changes upon an increase in DNA concentration. Inset: Plot of [DNA]/(εa–εf) versus [DNA] for absorption titration of DNA with complexes. Emission spectra of the complexes 1 (C) and 2 (D), arrow shows the fluorescence changes upon increasing DNA concentration. Inset: Plots of emission intensity I0/I versus [DNA]/[Complex] for the titration of complexes.
Fig. 9
Fig. 9
Molecular docking views of complex 6 against (A) E. coli (PDB: 5E8Q), (B) P. aeruginosa (PDB: 5EOE), (C) P. vulgaris (PDB: 5AVA), and (D) S. aureus (PDB: 5ELZ) receptors.
Fig. 10
Fig. 10
Molecular docking views of complexes 1 (A,B), 2 (C,D) and 6 (E,F) with DNA (PDB: 1BNA).
Fig. 11
Fig. 11
Molecular docking views of complexes 1 (A,B), 2 (C,D) and 3 (E,F) with SARS-CoV-2 receptor.
Fig. 12
Fig. 12
Molecular docking views of complexes 4 (A,B), 5 (C,D) and 6 (E,F) with SARS-CoV-2 receptor.
See this image and copyright information in PMC

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