Clinopodium nepeta Essential Oil and Its Major Constituents Pulegone and Menthone: Composition and Activity Against Verticillium dahliae, Phytophthora infestans, and Macrophomina phaseolina.

Fungal and oomycete phytopathogens account for 10%-20% of annual global crop losses, and the escalating resistance to synthetic fungicides has intensified demand for plant-derived alternatives. The essential oil (EO) of Clinopodium nepeta (L.) Kuntze, obtained by hydrodistillation from aerial parts harvested in northeastern Morocco, was profiled by gas chromatography-mass spectrometry (GC-MS) and evaluated for antifungal and anti-oomycete activity against Verticillium dahliae, Phytophthora infestans, and Macrophomina phaseolina using broth microdilution minimum inhibitory concentration (MIC) assays. The EO was dominated by two oxygenated monoterpene ketones, pulegone (42.16%) and menthone (41.43%), which were additionally evaluated as isolated compounds. The whole EO yielded MIC values of 31.25 µg/mL (P. infestans), 62.5 µg/mL (V. dahliae), and 125 µg/mL (M. phaseolina). Both isolated constituents outperformed the native matrix by 2- to 16-fold, revealing antagonistic interactions within the complex EO. Pulegone showed superior activity against V. dahliae and P. infestans, while menthone was more potent against M. phaseolina, a selectivity pattern consistent with the greater electrophilic reactivity of pulegone's α,β-unsaturated ketone (Michael acceptor) moiety. These findings identify pulegone and menthone as priority biopesticide candidates, pending formulation optimization, in planta validation, and toxicological assessment of pulegone under field-exposure conditions. Because the GC-MS analysis was performed on an achiral stationary phase, the enantiomeric composition of the oil was not determined; its constituents are therefore reported without stereodescriptors, and the compounds assayed as isolated agents were the commercial reference standards (R)-(+)-pulegone and (2S,5R)-(-)-menthone. The structure-activity relationship described here is consequently constitutional rather than configurational.