DNA gyrase inhibition by Ni(II)-Schiff base complexes via in silico molecular docking studies: Spectroscopic, DFT calculations and in vitro pharmacological assessment

Abstract

The current world's life-threatening illnesses have amplified multidrug resistance infections, bringing about immune system mayhem, thus, the quest for novel antimicrobial compounds with a broad spectrum of action. Four Ni(II) complexes, [Ni(YB)Cl]·2H₂O (C1), [Ni(YB)Br]·H₂O (C2), [Ni(YB)NO₃]·3H₂O (C3), [Ni(YB)COOCH₃]·2H₂O (C4) [HYB = 4-[(1E)-N-{2-[(Z)-(4-methoxybenzylidene)amino]ethyl}ethanimidoyl]benzene-1,3-diol], were synthesized. Analytical techniques like CHNS analysis, UV–Vis, FT-IR, molar conductance, XRD, ¹H NMR, and TGA/DTA were utilized for characterization. The calculated E_HOMO – E_LUMO energy gap and global reactivity descriptors of the compounds were performed by DFT calculations. The energy gap (ΔE) = E_HOMO – E_HOMO for the studied compounds HYB, C3, C4, C1, and C2 were found to be 1.736, 1.243, 1.221 1.217, and 1.193 eV respectively. The chelated complexes exhibited higher DPPH radical scavenging power than the corresponding free HYB ligand. Amongst the complexes, C2 displayed the highest scavenging ability (IC₅₀ = 2.59 ± 1.21 μM). Antimicrobial activities of the synthesized compounds were validated against bacterial strains: gram (+) E. faecalis and S. aureus; gram (−) P. aeruginosa and K. pneumoniae; and fungi: C. neoformans and C. albicans. C2 exhibited the most inhibition (MIC = 390.6 μg/mL) against P. aeruginosa and E. faecalis, while C1 acted as the most effective compound (MIC = 48.83 μg/mL) against the fungi strains. The docking study illustrated the highest binding affinity of −7.30 kcal/mol by C2 with P. aeruginosa (PDB: 8BN6), and C1 for the C. neoformans with −6.04 kcal/mol (PDB ID: 7T08) binding sites. Potential binding modes around the receptor's active sites were predicted by the in silico molecular docking studies.