Bioactive Constituentsfrom Roots of Diospyros undulata asPromising Antibacterial Agents─ In Vitro , In Silico , In Vivo , and Cytotoxic Studies

Pathogenic bacteria in aquaculture and agriculture remain a major challenge to food production and animal health, with substantial economic impacts worldwide. In this study, three previously undescribed naphthalene derivatives (1–3) and one naphthalenone (4), along with 12 known compounds, were isolated from the roots of Diospyros undulata. Naphthoquinones 5 and 7 exhibited potent antibacterial activity against several pathogens, including Staphylococcus aureus and Streptococcus agalactiae. Mechanistic studies indicated that these compounds disrupt bacterial membranes and inhibit biofilm formation. Molecular docking suggested interactions with key bacterial targets, including sortase A and FtsZ enzymes. In vivo studies in Nile tilapia demonstrated improved survival following infection when supplemented with D. undulata root extract. Additionally, compounds 5 and 12 showed cytotoxicity against human cancer cell lines, while compound 1 exhibited intracellular antioxidant activity. These findings highlight naphthoquinone derivatives from D. undulata as promising plant-derived antibacterial candidates and biomedical applications.