Design and development of salen-type Schiff bases as potential antivirus agents: Experimental and theoretical approach

Abstract

Five new salen-type Schiff base compounds (LH2-L4H2) have been designed and synthesized and their interaction with SARS-CoV-2, HIV virus and DNA polymerase IV have been studied by in silico approaches. The newly synthesized salentype Schiff base ligands have been derived from the condensation of substituted salicylaldehydes and ethylenediamine in MeOH. 1H and 13C NMR, FT-IR and UV-Vis spectral techniques have been applied in order to confirm the structural elucidation of the desired products. The crystal structure of the compound LH2 is determined by the single crystal X-ray diffraction. Density functional theory (DFT) calculations have been employed to evaluate the optimized electronic structure, HOMO-LUMO, energy gap, and global parameters. Extensive classical molecular dynamics simulations have been performed to investigate the consequences of docking of the synthesized ligand, LH2 on a protein moiety (PDB id: 7O46). Molecular docking studies have been performed on compounds (LH2-L4H2) to predict the binding mode and interactions between the ligands and the main protease of the SARS-CoV-2 (PDB ID: 7O46) for COVID-19 and HIV virus (PDB ID: 1UUI). The molecular docking results show that compounds (LH2-L4H2) with SARS-CoV-2 and HIV virus exhibit good binding affinity at binding site of receptor protein. As potential drug candidates, Swiss-ADME and target predictions (pharmacokinetics and drug-likeness prediction) analyses have also been studied and the results are compared with Chloroquine (CQ) and Hydroxychloroquine (HCQ) as anti-SARS-CoV-2 drugs. Salen-type ligands have also been docked into the DNA polymerase IV (PDB ID: 5YUX) for surface binding and intercalation. Overall, the present study offers the therapeutic potential for a series of compounds (LH2-L4H2) for biomedical applications with reference to coronavirus (SARS-CoV-2) and HIV virus.