Antibacterial Activity and in Silico Investigation of 2-[(3-Substitutedphenyl) Azomethine] Phenol as anti-SARS-CoV-2 Mpro and anti-Plasmodium falciparum Agents

Abstract

Imine derivatives are widely used in medicine for the treatment of several diseases causing human infections; we examined Schiff's bases derivatives: 2-[(3-methylphenyl) azomethine] phenol (L1), 2-[(3-chlorophenyl) azomethine] phenol (L2) and 2-[(3-nitrophenyl) azomethine] phenol (L3) against three human pathogenic bacterial strains according to the disk diffusion test. In addition, to revealing the importances of the in silico study of these derivatives, in particular the molecular docking which is based on the protein structures: the main protease 3CL of SARS-CoV-2 and the aminopeptidase of the M1 family. Also, a molecular dynamics simulation was performed to examine the structural stability of the best docked conformation. The evaluation of the global reactivity parameters of the molecular system of Schiff base derivatives was applied by the DFT method with the hybrid functional (B3LYP)/6-31G (d) basis set. The results of the antibacterial activity showed a strong activity in the presence of the L3 ligand against Escherichia coli (ATCC 25922) with a diameter inhibition zone equal to 11 +/- 0.61 mm. Molecular docking shows that the L3 ligand formed with protein targets more stable complexes by predicting interesting interactions: hydrogen, hydrophobic and electrostatic bonds with the residues of these targets 3CLpro and PfA-M1. Further, molecular dynamics simulations confirm a strong energy contribution with these interactions. Therefore, suggesting that our ligands could contribute to the development of anti-coronavirus-2 and anti-malarial drug properties.