Computational Drug Designing, Synthesis, Characterization and Anti-bacterial Activity Evaluation of Some Mixed Ligand–Metal Complexes of 2-hydroxybenzaldehydethiosemicarbazone as Primary Ligand

This paper reports the mixed ligand–metal complexes of CuSO(4)·5H(2)O and ZnSO(4)·7H(2)O with salicylaldehyde thiosemicarbazone (2-hydroxybenzaldehyde thiosemicarbazone) as primary ligand and imidazole (im), pyridine (py) and triphenylphosphine (PPh(3)) as secondary ligands through a general preparatory route. The ligand and complexes were characterized by FTIR, UV, (1)H-NMR and molar conductance techniques. Computational studies to know the physicochemical parameters, bioactivity scores, absorption, distribution, metabolism, excretion and toxicity (ADMET) properties were carried out through Molinspiration, SwissADME and admetSAR softwares. Molecular docking was perfomed with M(pro)of SARS-CoV-2 (PDB i.d.6LU7), Aspartate Kinase (PDB i.d.5YEI) and Transforming Growth Factor β (PDB i.d. 3KFD) using PyRx automated docking software. The antibacterial activity was tested using Agar well method. Computational findings revealed that almost all the complexes had clogP values less than 5 indicating their bioavailability. The bioactivity scores of the complexes were between moderate to good. The mixed ligand complexes having imidazole as secondary ligand displayed relatively high FCsp(3), indicating their potential as lead candidates. [Zn(C(8)H(9)N(3)OS)(PPh(3))(2)(SO(4))] and [Cu(C(8)H(9)N(3)OS)(im)(2)(SO(4))] exhibited appreciable binding affinity against the selected proteins. Furthermore, the molecular simulation findings with the ligated [Cu(C(8)H(9)N(3)OS)(im)(2)(SO(4))] and aspartate kinase showed compact folding, less deviations and significant stability. The stability of the ligand was further confirmed by the frontier molecular orbitals (FMOs) gap. The energy gap (− 0.423 eV) indicated molecular stability. The ligand was active against L. monocytogenes, S. aureus and E.coli having zone of inhibition of 11, 11 and 10 mm respectively. Among the complexes, [Cu(C(8)H(9)N(3)OS)(im)(2)(SO(4))] had the minimum inhibitory concentrations (MIC) ranging between 32 and 128 µg/mL against the selecetd bacterial strains. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42250-023-00640-4.