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

Abstract

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 in vitro. Among them, Q23 had better inhibitory activity against Phytophthora capsici (P. c.) with an EC50 of 6.68 μg/mL, outperforming the positive control azoxystrobin (Az, EC50= 72.60 μg/mL). Mechanistic studies indicated that Q23 inhibits fungal growth by disrupting hyphal integrity and inducing lipid peroxidation, as validated by SEM, FM, and MDA assays. Additionally, Q24 had better inhibitory activity against Xanthomonas axonopodis pv. citri (Xac), the pathogen responsible for citrus canker, with an EC50 of 5.13 μg/mL, surpassing the efficacy of the control agent thiodiazole-copper (TC, EC50 = 60.03 μg/mL). Further studies showed that Q24 inhibits Xac virulence by suppressing biofilm formation, reducing extracellular polysaccharides, and diminishing enzyme activity.