Aug 2026· Journal of Agricultural and Food Chemistry· Vol 74 33, pp.
26006-26016
· 0 citations· 48 references
Medicine
TL;DR
Mechanistic studies revealed that Q8 disrupted cell membrane integrity and inhibited succinate dehydrogenase (SDH) activity, with computational simulations suggesting a higher binding affinity for SDH than fluopyram.
Abstract
Twenty-three novel flavonol derivatives bearing a 1,2,3,4-tetrahydroquinoline (THQ) scaffold were designed and synthesized, and their antifungal activities against eight plant pathogenic fungi were evaluated. Several compounds exhibited 100% inhibition against Sclerotinia sclerotiorum and Phytophthora capsici (Pc). Among them, Q8 showed the most potent activity against Pc with an EC50 value of 4.1 μg mL-1, superior to azoxystrobin (69.0 μg mL-1) and fluopyram (123.2 μg mL-1). In vivo tests on chili fruits demonstrated that Q8 at 200 μg mL-1 provided superior curative and protective effects (73.7 and 80.8%) compared to azoxystrobin (53.0 and 54.4%). Mechanistic studies revealed that Q8 disrupted cell membrane integrity and inhibited succinate dehydrogenase (SDH) activity, with computational simulations suggesting a higher binding affinity for SDH than fluopyram. Safety evaluation showed no obvious adverse effects on seed germination or earthworm survival. Collectively, these results indicate that Q8 represents a promising lead compound for fungicide development.
Sterol 14α-demethylase (CYP51) and squalene epoxidase (SE) are rate-limiting enzymes in ergosterol biosynthesis, and their inhibition markedly retards fungal growth. A series of novel (1,2,4-triazol-1-yl)propan-2-ol derivatives were designed based on reported CYP51/SE inhibitor scaffolds. Bioassays demonstrated that compound 6o exhibited broad-spectrum antifungal activity, with EC50 values of 0.25, 0.38, and 0.49 mg/L against Valsa mali, Rhizoctonia solani, and Curvularia lunata, respectively. At 100 mg/L, compound 6o achieved 84.6% in vivo control efficacy against V. mali, comparable to difenoconazole (88.1%). Further studies revealed that compound 6o blocked ergosterol synthesis, damaged cell membrane integrity, elevated membrane permeability, and triggered intracellular ROS accumulation in V. mali. Enzyme activity tests, molecular docking, and qRT-PCR analyses suggested that compound 6o acts as a dual inhibitor of CYP51 and SE. Moreover, compound 6o exhibited good biosafety toward apple and rice seedlings. Collectively, compound 6o represents a promising lead for novel demethylation inhibitor fungicides for crop protection.
Jian-Wei Xue, Hai-Nan Luo, Shun-Bai Chen et al.· Journal of Agricultural and...· 0 citations
A series of 30 novel α-methylene-γ-butyrolactone (MBL) derivatives were designed and synthesized. Bioassays revealed that several compounds exhibited potent fungicidal activities against Valsa mali, Rhizoctonia solani, and Phytophthora capsici. A25 showed the highest activity against V. mali (EC50 = 0.70 mg/L). Against R. solani, A5 (EC50 = 0.94 mg/L) and A21 (EC50 = 0.69 mg/L) were highly active. Against P. capsici, A14 (EC50 = 0.69 mg/L), A21 (EC50 = 0.59 mg/L), and A24 (EC50 = 0.71 mg/L) displayed potent antioomycete activity. At 200 mg/L, A21 provided protective (88.9%) and curative (67.0%) effects in potted rice against R. solani as well as protective (91.0%) and curative (85.4%) effects on pepper plants against P. capsici. Mechanistic studies indicated that A21 blocks ATP synthesis and impairs energy metabolism. Toxicity assessment showed that A21 was nontoxic to earthworms and silkworms at the tested concentrations. This work provides insights for developing MBL derivatives as potential fungicides.
Deyou Yang, Heng Li, Jiaying Xu et al.· Journal of Agricultural and...· 0 citations
Findings suggested that compound 6m might be a potent candidate as a succinate dehydrogenase inhibitor (SDHI) against R. solani with strong protective and curative effects even at 50 μg/mL.
Bo Luo, Yan-Bing Wu, Qingsi Zhang et al.· Journal of Agricultural and...· 0 citations
Bacterial pathogens inflict substantial crop losses and economic damage, threatening global food security. Although antibacterial agents are available, their application is constrained by drug resistance, environmental hazards, and inadequate sustainability. Development of novel and effective antimicrobial agents has become urgent imperative. A series of morpholine-containing 1,3,4-thiadiazole derivatives were designed and synthesized. Compound H6 exhibited the most potent inhibitory activity against Xanthomonas oryzaepv oryzae (Xoo), with EC50 of 1.21 μg/mL-significantly lower than bismerthiazol (EC50 = 64.71 μg/mL) and thiodiazole-copper (EC50 = 63.94 μg/mL). Mechanistic studies revealed H6 inhibits biofilm and extracellular polysaccharide formation, disrupts membrane integrity, induces ROS accumulation, and promotes lipid peroxidation. Transcriptomic analysis demonstrated significant downregulation of key virulence genes (vgrG, accC, MCP), indicating attenuated pathogenicity. These results underscore H6 as a promising bactericidal agent, demonstrating considerable potential in sustainable management of plant bacterial diseases.
Mengzhi Yang, Cheng-Peng Li, Yue Zhou et al.· Journal of Agricultural and...· 0 citations
A series of 37 heterocycle-substituted α-methylene-γ-butyrolactone (MBL) derivatives were designed and synthesized. Bioassays showed that these derivatives possessed prominent fungicidal and bactericidal activities against Phytophthora capsici and Pseudomonas syringae pv actinidiae (Psa). Compound A6 exhibited the strongest antioomycete activity against P. capsici with an EC50 of 1.24 mg/L, presenting excellent in vivo protective (83.2%) and curative (81.2%) efficacies, while compound B12 exerted potent antibacterial activity against Psa (EC50 = 12.07 mg/L) with 72.3% protective efficacy against kiwifruit bacterial canker. Mechanistically, compound A6 functions mainly by binding to respiratory chain complex III. Notably, compound A6 caused no obvious adverse effects on chili pepper seed germination and plant growth at the tested concentrations of 100-400 mg/L. This study offers a basis for developing novel heterocycle-substituted MBL-derived agricultural antimicrobial agents.
Deyou Yang, Heng Li, Yong-Xin Liang et al.· Journal of Agricultural and...· 0 citations
The gem-difluoroalkylthio (−SCF2−) moiety has achieved great success in medicinal chemistry, but its application in agrochemicals remains underexplored because of synthetic challenges. Herein, we report a series of 1,2,4-triazole derivatives bearing the gem-difluoromethylthio group and evaluate their antifungal activities against ten phytopathogenic strains. Compound 7n exhibits potent broad-spectrum activity, with EC50 values of 0.007, 0.121, 0.122, and 0.068 μg/mL against Botrytis cinerea, Phytophthora capsici, Curvularia lunata, and Alternaria solani, respectively, outperforming tebuconazole. In vivo, 7n shows protective and curative efficacy comparable to tebuconazole on apple fruits, tomato fruits, and Suzhou Qing leaves. Mechanistic studies, including scanning electron microscopy (SEM), transcriptomics, qRT-PCR, and molecular docking, indicate that 7n disrupts mycelial morphology, interferes with membrane-associated processes, and inhibits sterol biosynthesis by targeting CYP51. These findings highlight the −SCF2– group as a promising scaffold for novel agricultural fungicides.
Jun-Qing Liang, Yu-Long Miao, Xi Cheng et al.· Journal of Agricultural and...· 0 citations
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