Synthesis, Characterization, and Antimicrobial Activity of Hydrazino Triazole–Based Schiff Base Ligands and Their Oxovanadium (IV) Complexes and the Inhibitory Roles Against SARS-CoV-2 Using Molecular Docking, Dynamics, and ADMET Profiling

Abstract

This study addresses the structural analysis and bioactivity evaluation of newly synthesized hydrazino triazole-based Schiff base ligands (SS and SA) and their oxovanadium (IV) complexes (DS and DA). The synthesized ligands and complexes were characterized using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) patterns, and ultraviolet–visible (UV–Vis) spectroscopy. The XRD patterns of the complexes indicate the presence of tiny polycrystalline phases, with a crystallite size of 17.538 nm for DS. Biological activity was assessed in vitro against bacterial pathogens Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and the fungal species Candida albicans. Complex DA demonstrated prominent antimicrobial activity with a ZOI value of 12, 9, 8, 7, and 7 mm, respectively, against the tested bacterial and fungal species, and the complex DS has promising antioxidant activity with an IC₅₀ value of 46.23 μg/mL. Alpha-amylase inhibitory effects were relatively low for SA and SS, with a mean inhibitory percent value of 7.33% and 8.29%, while DA and DS demonstrated the highest inhibitions of 16.18% and 11.27%, respectively, highlighting their limited potential as alpha-amylase inhibitors. The docking scores of triazole, hydrazino triazole, and Schiff base ligands (SA and SS) with SARS-CoV-2 Mpro were −5.91, −6.27, −11.47, and −10.15 kcal/mol, respectively, with SA exhibiting the better binding affinity, suggesting its prominent activity. Molecular dynamic (MD) simulations over 100 ns, assessing parameters such as RMSD, RMSF, Rg, SASA, and H-bonds, revealed that SS maintained greater stability than the other ligands. The end-point energy (MM/PBSA) of the Schiff base ligand SS with Mpro was calculated as −18.25 kcal/mol. The ADMET parameters, docking scores, and MD simulation results suggested SS as a potential drug candidate against COVID-19. This study highlights the multitarget activity of Schiff bases and their compounds, emphasizing the importance of future research on related compounds to unlock their full therapeutic potential across diverse medical applications.