Botrytis cinerea is a phytopathogenic fungus that causes serious damage to the agricultural industry by infecting various important crops. 2-allylphenol has been used in China as a fungicide for more than a decade, and it has been shown that is a respiration inhibitor. A series of derivatives of 2-allylphenol were synthesized and their activity against B. cinerea was evaluated by measuring mycelial growth inhibition. Results indicate that small changes in the chemical structure or the addition of substituent groups in the aromatic ring induce important variations in activity. For example, changing the hydroxyl group by methoxy or acetyl groups produces dramatic increases in mycelial growth inhibition, i.e., the IC₅₀ value of 2-allylphenol decreases from 68 to 2 and 1 μg mL⁻¹. In addition, it was found that the most active derivatives induce the inhibition of Bcaox expression in the early stages of B. cinerea conidia germination. This gene is associated with the activation of the alternative oxidase enzyme (AOX), which allows fungus respiration to continue in the presence of respiratory inhibitors. Thus, it seems that 2-allylphenol derivatives can inhibit the normal and alternative respiratory pathway of B. cinerea. Therefore, we believe that these compounds are a very attractive platform for the development of antifungal agents against B. cinerea.

The phytopathogenic fungus Botrytis cinerea, which causes gray mold disease, has become a limiting factor on agricultural production. B. cinerea field control is made mainly using chemical fungicides, which has led to the spreading of resistant populations of this fungus. Thus, the quest of new fungicides molecules has been focused on synthesis of natural product-inspired compounds. The main aim of this work is to synthesize prenylated phenol derivatives and to assess their potential application as antifungal agents with minimal phytotoxic effects. Thus, new prenylphenols (4, 5, and 7) have been obtained by microwave irradiation with yields ranging from 2.4% to 42.9%, whereas compounds 8 and 9 were synthesized with yields of 25.6% and 54.1%, respectively. The effect of different concentrations of these compounds on B. cinerea spore germination, and their phytotoxic effect on tomato (Solanum lycopersicum L.) seed germination and root growth, were evaluated. Obtained results indicate that biological activities of all tested compounds are concentration-dependent. Interestingly, compound 7 exhibits the highest antifungal activity against B. cinerea spores (IC₅₀ < 50 µg/mL) with minimal phytotoxicity on tomato seed germination and root growth. In contrast, compounds 2 and 3 are active against spores (IC₅₀ = 461 and 325 µg/mL, respectively) but, at the same time, their phytotoxicity is important at the highest concentrations. These results indicated that the presence of hydroxyl and methyl substituents on the aromatic ring of these compounds induces variations in biological activities, and compound 7 could be a promising candidate as a sporicidal agent.

A series of ten geranylated benzaldehydes (11–20) was designed, synthesized via Suzuki cross-coupling for the C–C series and S_N2 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.