Chemical profiling and antimicrobial activity of the leaf essential oil of Vepris nobilis (Delile) Mziray : in silico evaluation of the major constituent, germacrene D

Abstract

Antimicrobial resistance is a growing global health challenge, highlighting the need for new bioactive compounds from medicinal plants. Vepris nobilis is traditionally used in East Africa for treating infections and respiratory disorders; however, its essential oil (EO) composition and antimicrobial mechanisms remain poorly characterized. This study investigated the chemical composition and antimicrobial activity of V. nobilis EO, along with an in silico evaluation of its major constituent, germacrene D. The EO was extracted by hydrodistillation and analyzed using gas chromatography-mass spectrometry (GC–MS). Its antimicrobial activity was evaluated against 26 bacterial and 4 fungal strains using disc diffusion, broth microdilution, and MBC/MFC (Minimum Bactericidal Concentration/Minimum Fungicidal Concentration) assays. Germacrene D showed stronger activity than the EO, particularly against both multidrug resistant (MDR) and non-MDR Gram-negative bacterial strains (MIC = 10 µg/mL), with bactericidal and fungicidal effect. Molecular docking of germacrene D against two clinically relevant enzymes—dehydrosqualene synthase (CrtM) from Staphylococcus aureus and SWISS-modeled sterol 14-α-demethylase (CYP51) from Penicillium funiculosum—suggested potential interactions with both targets, with a favorable predicted binding affinity for CrtM (−7.654 kcal/mol) and for CYP51 (−5.898 kcal/mol). These findings provide preliminary insights into a possible antimicrobial mechanism, although experimental validation is needed to confirm this hypothesis. ADMET analysis suggested favorable drug-like properties despite limited solubility. These findings provide scientific support for the traditional use of V. nobilis leaves in the treatment of respiratory infections and highlight germacrene D as a promising lead compound for further antimicrobial development.