<![CDATA[Zanthoxylum avicennae (Lam.) DC. is an aromatic, prickly Rutaceae shrub or small tree whose oil-gland-bearing fruits have a characteristic pepper-like aroma and a history of traditional medicinal use in Southeast Asia. Because the chemical profile and integrated bioactivity of fruit essential oil (EO) from central Vietnam remain insufficiently characterized, this study examined the chemical composition and in vitro bioactivities of the fruit EO collected in Quang Nam, Vietnam. A total of 24 volatile components were identified via GC-MS, with the major components being estragole, eucalyptol, β-linalool, and caryophyllene oxide. Furthermore, the oil exhibited antimicrobial efficacy against B. cereus, S. aureus, A. niger, A. brassicicola and P. capsici, with particular antifungal activity against P. capsici (MIC = 62.5 µg/mL). The oil suppressed S. aureus biofilm formation in a dose-dependent manner (IC50 = 473.2 µg/mL). Cytotoxicity was weak against A549 cells and negligible within the tested range against B16-F10 and Huh-7 cells. Molecular docking identified (+)-(S)-terpinen-4-ol as the best-scoring ligand for CYP51 and Hsp90. A 100-ns molecular dynamics simulation indicated that the CYP51-(+)-(S)-terpinen-4-ol complex remained structurally stable, with persistent but conformationally flexible contacts. MM/GBSA analysis yielded a favorable mean binding energy of −33.63 ± 4.92 kcal/mol, dominated by van der Waals interactions. Overall, Z. avicennae fruit EO showed promising in vitro antifungal, antioxidant, and anti-biofilm activities that warrant further constituent-specific, mechanistic, toxicity, and in vivo validation.]]>
