Design, Synthesis, and Biological Activity Evaluation of Flavonol Derivatives Containing Piperazine and Piperidine Thiourea

A series of flavonol derivatives incorporating piperazine and piperidine thiourea moieties were designed and synthesized. The compounds were evaluated for their activity against 8 plant pathogenic fungi and 6 plant pathogenic bacteria <i>in vitro</i>. Among them, <b>Q23</b> had better inhibitory activity against <i>Phytophthora capsici</i> (<i>P. c.</i>) with an EC₅₀ of 6.68 μg/mL, outperforming the positive control azoxystrobin (<b>Az</b>, EC₅₀= 72.60 μg/mL). Mechanistic studies indicated that <b>Q23</b> inhibits fungal growth by disrupting hyphal integrity and inducing lipid peroxidation, as validated by SEM, FM, and MDA assays. Additionally, <b>Q24</b> had better inhibitory activity against <i>Xanthomonas axonopodis</i> <i>pv.</i> <i>citri</i> (<i>Xac</i>), the pathogen responsible for citrus canker, with an EC₅₀ of 5.13 μg/mL, surpassing the efficacy of the control agent thiodiazole-copper (<b>TC</b>, EC₅₀ = 60.03 μg/mL). Further studies showed that <b>Q24</b> inhibits <i>Xac</i> virulence by suppressing biofilm formation, reducing extracellular polysaccharides, and diminishing enzyme activity.