Targeting Botrytis cinerea: Hybrid molecules combining limonene and Pyridin-2-amine scaffolds as promising antifungal candidates

Botrytis cinerea is a major necrotrophic fungal pathogen responsible for grey mould disease, affecting crops at various stages of production and storage. The search for alternative antifungal agents is crucial to mitigate the environmental and health risks associated with synthetic fungicides. Among the potential candidates, monoterpenes and aromatic N -benzylamines have emerged as promising non-toxic alternatives. This study reports on the synthesis and in vitro antifungal evaluation of a series of aromatic N -benzylamines, along with hybrid molecules incorporating limonene and aromatic amine fragments. Notably, compounds featuring pyridin-2-amine moieties exhibited the highest antifungal activity, and hybrid molecule 22 had the lowest EC 50 value (12.7 μg/mL). Molecular docking studies suggest that SDH enzyme could be one of the potential action targets of the hybrid molecules. These results highlight compound 22 as a promising candidate for further fungicidal development. • N -benzylanilines and N -benzylpyridin-2-amines synthesized by N -alkylation reaction • Synthesis of hybrid molecules containing limonene and pyridine-2-amine scaffolds • Hybrid molecule 22 fully inhibited B. cinerea at 25 μg/mL; better than commercial triclosan. • Compound 22 exhibited an EC 50 value of 14.7 μg/mL. • Molecular docking suggests that SDH could be the target of compound 22.