Synthesis, Antibacterial Properties and Molecular Docking of Nitrobenzoylthiourea Compounds and their Copper(II) Complex

The rise of multidrug-resistant microbial pathogens has increased the demand for highly effective antibiotics. Five nitrobenzoylthiourea ligands (1–5) with amino acid side chains and their corresponding Cu(II) complexes (6–10) were synthesised with yields ranging from 43% to 90%. The successful synthesis of ligands 1-5 were confirmed by the absence of the ν(NCS) stretching band and the presence of the ν(NH) band, indicating the complete reaction of all (NCS) with a series of amino acids as well as the appearance of two N-H signals in the 1H NMR spectra of all the synthesised ligands. On the other hand, the shift of the (C=O) carboxylic peaks in the Cu(II) complexes suggested successful coordination of ligands to the metal ion via the carboxylate group. The antibacterial activities of these compounds were tested against six bacteria: Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa using the disc diffusion method. The Cu(II) complexes (6-10) exhibited enhanced antibacterial activity compared to the ligands  (1-5), especially against gram-negative bacteria (E. coli, K. pneumoniae, and P. aeruginosa). For example, compound 4 showed moderate activity against K. pneumoniae with a 14 mm inhibition zone while its Cu(II) complexes, 8 recorded better inhibition  against K. pneumoniae with a 16 mm inhibition zone. Molecular docking studies on all complexes (6-10) also revealed higher binding affinity with targeted proteins with binding energy between -10.4 kcal/mol to -9.0 kcal/mol, in comparison with ligand 2 and 4 with the binding energy of only -7.7 kcal/mol (against S. aureus) and -6.9 kcal/mol (against K. pneumoniae). The enhanced antibacterial activity of all complexes correlates with the higher binding affinity obtained for all complexes. Hence, this study concludes that the nitrobenzoylthiourea derivatives, and particularly their Cu(II) complexes can show potential as antibacterial agent although more thorough investigation are required to develop these compounds into useful drugs.