Investigation of biological activity of oxindole semicarbazones based copper (II) complexes: Synthesis, antimicrobial activities and molecular modelling

Abstract

Copper (II) acetate reacted with 2-oxindole semicarbazone (2-Hoxsc, H¹L), 3-methyl 2-oxindole semicarbazone (3-MeHoxsc, H²L) and 6-Chloro-2-oxindole semicarbazone (6-ClHoxsc, H³L) in 1:2 (M:L) molar ratio to form complexes of general formula, [Cu(L₂)] (¹L, 1; ²L 2; ³L 3. Stoichiometric ratio of complexes was established using UV–Vis spectroscopy. All the complexes were characterised by the CHN analysis, IR, ESR spectroscopy and Mass spectrometry. From the ESR spectrum, g values obtained (g_‖ = 2.20; g_⊥ = 2.05) for complex 2 confirms axial symmetry for this complex, whereas a broad isotropic signal in 1 and 3 (g_iso = 2.060, 1; 2.057, 3) indicates extensive exchange coupling. All the synthesized compounds (ligands and complexes) complexes were examined for their anti-tubercular activity against M. tuberculosis H37RV strain. Compounds were also tested for their anti-bacterial (B. subtilis, K. pneumonia) and antifungal (C. auris, C. albicans) activities. Biological investigations revealed that the antimicrobial activities (anti-TB, antibacterial and antifungal) of ligands get improved on complexation with Cu (II) due to formation of chelate ring, which can make the ligand a more powerful biological agent. Complex 3 has shown excellent anti-TB (MIC = 1.6 g/ml) and antibacterial (ZOI = 26 mm at 5 mg/mL) activities. Strong binding of complex 3 was observed (K_b = 24.22 × 10⁵ M⁻¹) with Human Serum Albumin (HSA) using fluorescence spectroscopy. Molecular modelling of complex 3 was also done with the active site of amino acid of M. tuberculosis enoyl reductase. The minimal binding energy of −10.1 kcal/mol indicated significant intermolecular interaction between M. tuberculosis enoyl reductase and complex 3 and is in well agreement with experimental data.