In
an ongoing effort to explore more potent antifungal pogostone
(Po) analogues, we maintained the previously identified 3-acetyl-4-hydroxy-2-pyrone
core motif while synthesizing a series of Po analogues with variations
in the alkyl side chain. The in vitro bioassay results
revealed that compound 21 was the most potent antifungal
analogue with an EC50 value of 1.1 μg/mL against Sclerotinia sclerotiorum (Lib.) de Bary. Meanwhile,
its Cu(II) complex 34 manifested significantly enhanced
antibacterial activity against Xanthomonas campestris
pv campestris (Xcc) with a minimum
inhibitory concentration (MIC) value of 300 μg/mL compared with 21 (MIC = 700 μg/mL). Complex 34 exhibited
a striking preventive effect against S. sclerotiorum and Xcc in rape leaves, with control efficacies
of 98.8% (50 μg/mL) and 80.7% (1000 μg/mL), respectively.
The 3D-QSAR models generated using Topomer comparative molecular field
analysis indicated that a shorter alkyl chain (carbon atom number
<8), terminal rings, or electron-deficient groups on the alkyl
side chain are beneficial for antifungal potency. Further, bioassay
results revealed that the component of 21 in complex 34 dominated the antifungal activity, but the introduction
of Cu(II) significantly enhanced its antibacterial activity. The toxicological
observations demonstrated that 21 could induce abnormal
mitochondrial morphology, loss of mitochondrial membrane potential,
and reactive oxygen species (ROS) accumulation in S.
sclerotiorum. The enzyme assay results showed that 21 is a moderate promiscuous inhibitor of mitochondrial complexes
II and III. Besides, the introduction of Cu(II) to 34 could promote the disruption of the cell membrane and intracellular
proteins and the ROS level in Xcc compared with 21. In summary, these results highlight the potential of 34 as a dual antifungal and antibacterial biocide for controlling
rape diseases or as a promising candidate for further optimization.