Miao Li

A series of amide-coumarin derivatives ( M1 – M20 ) were synthesized and evaluated for antibacterial activity against Xanthomonas oryzae pv. oryzicola (Xoc) , Xanthomonas campestris pv. citri (Xac) and Pseudomonas syringae pv. actinidiae (Psa) . Although all compounds showed moderate activity, M13 exhibited the strongest inhibition against Xoc with a half-maximal effective concentration of 59.3 mg/L, outperforming the controls thiodiazole copper and zinc thiazole. Density functional theory and electrostatic potential analyses were performed to elucidate the electronic structures. Molecular docking indicated that the amino group of M13 acts as a hydrogen-bond donor, interacting with residues LEU372 and GLU77. Furthermore, morphological changes in Xoc cells treated with M13 were observed using scanning electron microscopy.

BACKGROUND: The increasing prevalence of phytopathogenic bacteria, such as Xanthomonas oryzae pv. oryzicola ( Xoc ), Xanthomonas axonopodis pv. citri ( Xac ) and Pseudomonas syringae pv. actinidiae ( Psa ), poses a serious threat to global agricultural productivity, underscoring the urgent need for novel antibacterial agents with distinct mechanisms of action. This study designed, synthesized, and evaluated a series of phosphonyl‐substituted vanillyl sulfonyl hydrazide derivatives for their antibacterial activity and to elucidate the potential mechanisms of action of the most active compound. RESULTS: In total, 26 novel phosphonyl‐substituted vanillyl sulfonyl hydrazide derivatives C were synthesized and structurally confirmed. Bioassays revealed that most compounds exhibited moderate to good antibacterial activity against the tested pathogens. Notably, compound C02 exhibited the most potent activity against Xoc , with a half‐maximal effective concentration (EC ₅₀ ) value of 28.2 mg/L. Mechanistic studies revealed that C02 binds to the active cavity of the target protein (Protein Data Bank code: 4Z8V), forming stable interactions. Further analysis showed that C02 is highly chemically reactive and stable, disrupts bacterial cell membrane integrity (causing wrinkling and rupture), and considerably inhibits the activity of the key metabolic enzymes. Proteomic analysis demonstrated that C02 treatment broadly disrupts bacterial metabolic pathways, including energy metabolism, amino acid synthesis, and cell membrane biosynthesis. CONCLUSION: Compound C02 exerts its potent antibacterial effects through a multi‐mechanism action involving membrane disruption and interference with multiple core metabolic processes. These findings provide a theoretical foundation and experimental evidence for developing novel antibacterial agents based on the phosphate‐containing vanillin sulfonyl hydrazide scaffold, significantly advancing the field by identifying a promising lead compound with a well‐characterized, multi‐faceted mode of action. © 2026 Society of Chemical Industry.

In this study, we successfully synthesized a series of new phosphonate derivatives by coupling the phosphate backbone with sulfonyl lipids via an organic synthesis route. During in vitro antibacterial activity assays, all of these derivatives exhibited significant inhibitory effects, with compound M25 showing particularly superior activity. Experimental data indicate that compound M25 markedly enhances the permeability of the bacterial cell membrane, leading to damage to the Xanthomonas oryzaepv oryzicola (Xoc) membrane and effectively inhibiting bacterial growth and proliferation. This important finding not only reveals the mode of action of compound M25 but also provides a solid scientific foundation for the development of novel antibacterial agents in the future.

Pesticide resistance in plant bacterial pathogens necessitates new antibiotic alternatives. Herein, novel sulfonamide-containing phosphonate compounds were synthesized, with their antibacterial activity and mechanism systematically investigated. Bioassays showed that compound A2 exhibited the strongest activity against Xanthomonas oryzae pv oryzae (Xoo), with an EC₅₀ of 9.9 μg/mL. Mechanistic studies revealed that A2 disrupts bacterial cell membrane integrity (via SEM and EC measurements), enhances host resistance by upregulating catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) activities, and dysregulates proteins involved in streptomycin biosynthesis, purine metabolism, and ribosomal pathways, thereby inhibiting bacterial protein synthesis and inducing cell death. These findings highlight sulfonamide-containing phosphonates as promising antibacterial agents against plant bacterial diseases.

Heavy metal contamination in orchards has received increasing attention as people pay more attention to food safety issues. In this study, the levels of six heavy metals (Cu, Ni, Pb, Zn, Cd and Cr) in soil and fruit (peel and pulp) of 70 kiwifruit orchards in Xiuwen County, Guizhou Province, China, were investigated by inductively coupled plasma mass spectrometry (ICP-MS), and correlation analyses as well as dietary risk assessment. The results showed that the mean concentrations of the six heavy metals (Cu, Ni, Pb, Zn, Cd and Cr) ranged from 0.41-104.02 mg kg-1 in soil, <0.01-2.15 mg kg-1 in peel and <0.01-0.23 mg kg-1 in flesh, with the heavy metal content in flesh being significantly lower than that in peel. Among the 70 soil samples in this study, some samples of Cd, Ni, Cu and Zn exceeded the secondary standard for soil environmental quality in China, and the proportions of Cu, Ni, Pb, Zn, Cd and Cr exceeding the geochemical soil background values in Guizhou were 72.86%, 72.86%, 64.29%, 52.86%, 48.57% and 37.14%, respectively. The results of the correlation analysis indicated that the higher the Cu content in the soil, the more favorable the transfer and enrichment of Cr, Cd, Cu, Zn and Ni to kiwifruit fruit, and the less favorable the enrichment of Pb. The results of the food safety risk assessment indicated that none of the six heavy metals in kiwifruit posed a significant risk to human health. This study can provide a reference for the regular investigation of heavy metal pollution in kiwi orchards and the long-term safety of kiwifruit.

The formation of bacterial biofilms enhances pathogen resistance, reducing the efficacy of traditional antibacterial agents. Consequently, developing new and efficient biofilm inhibitors is critical. Herein, a series of sulfonamide derivatives containing α-aminophosphonate fragments were designed, synthesized, and evaluated for antimicrobial activities. In vitro bioassay revealed the superior efficacy of compound A20 (EC₅₀ = 26.6 μg mL^-1) over the commercial bactericide thiodiazole copper (EC₅₀ = 82.5 μg mL^-1) against Xanthomonas axonopodis pv. citri (Xac). Further studies demonstrated that A20 effectively inhibited Xac biofilm formation and reduced multiple virulence factors, including extracellular enzyme activity, motility, and extracellular polysaccharide (EPS) production. These excellent properties are undoubtedly transmitted to in vivo activity, yielding preventive efficacies of 75.32% and 50.28% against citrus bacterial canker at 200 μg mL^-1, surpassing those of thiodiazole copper (57.52% and 43.83%). These findings indicate that inhibiting biofilm formation represents a promising strategy for developing novel antibacterial agents to manage persistent plant bacterial diseases.

Bacterial biofilms serve as a natural barrier, enabling bacteria residing within them to exist and potentially amplify bacterial resistance by shielding themselves from bactericide exposure. Despite considerable efforts directed toward inhibiting bacterial growth, research has overlooked bacterial biofilms to a significant extent, leading to the frequent deficiency of traditional antimicrobials in inhibiting such biofilms. This necessitates the development of antimicrobials capable of inhibiting biofilms for effective antibacterial intervention. Herein, we have developed a new bacteriostatic agent, A₆, which has demonstrated the capability of inhibiting biofilm formation. It achieved a biofilm inhibition rate of 72.76% at a concentration of 47.94 μg/mL (2.0 EC₅₀). Mechanistic studies revealed that A₆ inhibits extracellular polymeric substances (EPS) production and bacterial motility, both critical for bacterial virulence, biofilm formation, maturation, or plant cell wall degradation. Additionally, the conductivity and protein leakage experiments demonstrated that compound A₆ significantly affected various physiological processes of Xoc. In summary, A₆ presents a promising antimicrobial solution by simultaneously inhibiting biofilms, addressing a crucial aspect of bacterial plant diseases. Graphical abstract A series of phosphosulfanilamide derivatives were synthesized using a solvent-free one-pot method. Compound A₆ effectively inhibits bacterial biofilm formation, bacterial motility, and EPS production.

Double-activation catalytic systems are potent for making complex molecules in natural products and pharmaceutical fields, yet regulating the synergistic effect between the two catalysts is extremely challenging. Herein, a Cu/Ag double-activation catalysis that enabled the cascade Mannich/5-endo-dig cyclization was developed for the synthesis of a variety of spiro-cyclopentene-oxindole derivatives with three adjacent quaternary centers (up to 88% yield, >19:1 dr). Mechanistic investigations showed that it was not base-catalyzed, a single-metal catalyst showed poor performance, and the bimetallic catalyst was vital for highly efficient conversion.