Design and Synthesis of Geranylated Benzaldehydes: Evaluation of Antifungal Activities Against Botrytis cinerea and Phytophthora cinnamomi.

A series of ten geranylated benzaldehydes (11-20) was designed, synthesized via Suzuki cross-coupling for the C-C series and SN2 substitution for the C-O derivatives, and structurally characterized. The antifungal activity of all compounds against the phytopathogens Botrytis cinerea and Phytophthora cinnamomi, two important plant pathogens associated with substantial agricultural and economic losses worldwide, was evaluated in vitro using a mycelial growth inhibition assay. Dose-response treatment of the data indicates that (E)-2-((3,7-dimethylocta-2,6-dien-1-yl)oxy)-5-hydroxybenzaldehyde (19) is the most active compound exhibiting EC50 values of 83 µg/mL and 7.34 µg/mL against B. cinerea and P. cinnamomi, respectively. To gain insight into the molecular basis of the observed antifungal activity, molecular docking studies were performed targeting the active site of succinate dehydrogenase (SDH, PDB ID: 2FBW), a key enzyme in the mitochondrial respiratory chain and a validated fungicide target. The calculated docking scores ranged from -6.0 to -7.5 kcal/mol, with compound 19 showing the highest binding affinity. Docking analysis reveals that compound 19 is stabilized within the SDH binding pocket through a network of hydrogen bonding and π-cation interactions involving the heme prosthetic group and key amino acid residues, providing a plausible structural rationale for its high antifungal activity, particularly against P. cinnamomi.