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

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