In this study, we investigated the antibacterial activity of 27 amino acid Schiff base copper(II) complexes and explored the relationships between molecular properties and antibacterial efficacy. Using density functional theory and protein-ligand docking calculations, we analyzed descriptors such as hydrophobicity, electronic energy (EE), polarizability, and topological polar surface area, alongside experimental and calculated LogP (logarithmic octanol-water partition coefficient) values. Antibacterial activity was evaluated against five bacterial strains, including Escherichia coli and Staphylococcus aureus. Active complexes were predominantly found within a narrow LogP range (1.0 to 2.0), and tended to show moderately high polarizability and EE values. Docking scores were generally higher for active compounds, though not strictly predictive of biological outcomes. Notably, tryptophan-containing complexes demonstrated potent activity despite falling outside typical electronic thresholds, which may be explained by favorable local interactions such as π–π stacking and CH–π interactions. Quantum chemical interaction energy calculations supported the energetic favorability of these local aromatic contacts. These results highlight the importance of combining global electronic descriptors with local binding interactions in evaluating biological activity. This integrated computational–experimental approach provides a valuable framework for rational design of bioactive metal complexes with improved antibacterial properties. Graphical abstract

Shigellosis is a pathological condition that affects the digestive system and possibly causes diarrhoea. Shigella species, which are responsible for this disease, are highly contagious and spread through contaminated food and water. The increasing development of resistance by Shigella species necessitates the urgent need to search for new therapies against diarrhoea-causing shigellosis. The scientific validation of medicinal plants, such as Diospyros gilletii, which is used for the traditional treatment of diarrhoeal conditions is worthwhile. The present study aims to investigate the antibacterial activity of extracts from D. gilletii against selected Shigella species. Extracts from D. gilletii stem bark were prepared by maceration using various solvents. The antibacterial activity of D. gilletii extracts was evaluated in Shigella dysenteriae, S. flexneri, S. boydii, and S. sonnei using a microdilution method, whereas a cytotoxicity test was performed on Vero and Raw cells using resazurin-based colorimetric assays. Bacterial membrane-permeability studies were evaluated using propidium iodide (PI)- and 1-N-phenyl-naphthylamine (NPN)-uptake assays, whereas inhibition and eradication tests on bacterial biofilms were carried out by spectrophotometry. As a result, methanol, ethanol and hydroethanol (water: ethanol; 30:70, v/v) extracts of D. gilletii inhibited the growth of S. boydii, S. flexneri and S. sonnei, with minimum inhibitory concentration (MIC) values ranging from 125 to 500 µg/mL, without toxicity to Vero and Raw cells. Time-kill kinetics revealed bactericidal orientation at 2 MIC and 4 MIC and a bacteriostatic outcome at 1/2 MIC. The mechanistic basis of antibacterial action revealed that D. gilletii extracts inhibited and eradicated Shigella biofilms and promoted the accumulation of NPN and PI within the inner and outer membranes of bacteria to increase membrane permeability, thereby causing membrane damage. This novel contribution toward the antibacterial mechanisms of action of D. gilletii extracts against Shigella species substantiates the use of this plant in the traditional treatment of infectious diarrhoea.