Phytopathogenic bacteria are responsible for devastating agricultural losses globally. However, the chemical control of these pathogens is compromised by escalating resistance, environmental pollution, antibiotic resistance gene transfer, and a scarcity of validated antibacterial targets. To fill this gap, this review provides a critical and chemically-focused discussion of recent breakthroughs, aiming to bridge the gap between synthetic innovation, modern target discovery, and rational, data-driven design. Herein, we delineate emerging antibacterial compounds, emphasizing their structural diversity, structure-activity relationships, novel modes of action, and molecular targets. Furthermore, advanced methodologies for discovering and validating antibacterial targets are thoroughly examined, along with deep mechanistic insights. A forward-looking perspective on transformative approaches is also provided. This review aims to guide interdisciplinary efforts and stimulate the development of effective, sustainable, and environmentally friendly next-generation phytobactericides by offering the analysis urgently required by the field.

Plant bacterial diseases cause significant harm to agricultural production because of their frequent, intermittent and regional outbreaks. Currently, chemical control is still a more effective method for bacterial disease. To develop new, efficient and safe antibacterial agrochemicals, we summarize the research progress of compounds with antibacterial activities in the past ten years, classify them according to their active skeletons, and discuss their structure-activity relationships and mechanisms of action. Finally, the development trend of antibacterial agrochemicals was prospected. This review provides valuable information for the development of antibacterial agrochemicals.

Abstract In recent years, tea leaf spot, caused by the fungus Epicoccum sorghinum, adversely affects both the yield and quality of tea in China. Transient overexpression and antisense oligonucleotide (AsODN) assays revealed that upregulating CsMYB1, a transcription factor located in the nucleus, enhances resistance to E. sorghinum infection in tea leaves. Overexpression of CsMYB1 in transgenic Nicotiana benthamiana conferred resistance to Botrytis cinerea. Multi-omics assays of transiently overexpressed CsMYB1 in tea leaves indicated that CsMYB1 induces the expression of numerous disease resistance genes. DNA affinity purification sequencing assay indicated that CsMYB1 can activate the expression of the disease resistance gene pectinesterase/pectinesterase inhibitor 41 (CsPME41). β-glucuronidase and dual-luciferase assays showed that csi-miR858-3p_L-1 targets and cleaves CsMYB1. Moreover, transient overexpression and AsODN assays in tea leaves and transgenic csi-miR858-3p_L-1 N. benthamiana plants indicated that increasing csi-miR858-3p_L-1 levels heightens susceptibility to E. sorghinum in tea leaves. The relative expression levels of CsMYB1, CsPME41, and csi-miR858-3p_L-1 in tea leaves exhibited distinct spatial and temporal patterns in response to E. sorghinum invasion. This study reveals that the csi-miR858-3p_L-1–CsMYB1–CsPME41 module plays a role in the disease resistance response of tea plants to E. sorghinum infection, providing crucial data for resistance breeding.

Global spread of weeds resistant to conventional herbicide modes of action threatens sustainable weed management. Cinmethylin, a decades-old herbicide with a unique molecular basis, has re-emerged for controlling resistant grass weeds, but remains commercialized as an enantiomeric mixture owing to challenges in asymmetric 1,4-cineole construction and unclear stereoselective bioactivity. Here, we report an efficient chiral N-heterocyclic carbene-mediated kinetic resolution of 2-hydroxy-1,4-cineole, a key cinmethylin precursor. X-ray crystallography establishes the absolute configurations of both enantiomers, which are converted into enantiomer-enriched cinmethylin. Herbicidal assays against ten grass weeds, crop safety tests, receptor binding, and multiomics analyses identify (1S,2R,4R)-cinmethylin as the eutomer, with superior pre- and postemergence activity and excellent crop selectivity. It more strongly inhibits and binds fatty acid thioesterase via Arg176, blocking fatty acid release and reprogramming hormone signaling. This work enables optimized cinmethylin use and reduces inactive distomer inputs.

Megoura crassicauda, a sap-feeder on legumes, remains a persistent threat, yet current control depends largely on neonicotinoids that pose serious risks to beneficial pollinators. We herein describe a set of new pyrido[1,2-a]pyrimidinone derivatives bearing a carbamate moiety attached via a methylene spacer at the 2-position. Insecticidal bioassays identified H3 as the most potent analogue against M. crassicauda, comparable to the commercial standard TFM. Encouragingly, H3 exhibited remarkably low toxicity to honeybees, with acute oral and contact LD50 values of 24.0 and 35.1 μg a.i./bee, respectively, which were markedly higher than those of TFM. Mechanistic studies combining proteomics, enzymatic assays, and molecular docking consistently suggested that H3 disrupts neuronal homeostasis via interfering with nAChR and AChE activity, leading to insect mortality. This work provides a promising and bee-safe lead for sustainable pest management, offering a new molecular template for the development of highly selective insecticides.

As a bioisostere of oxygen/sulfur, selenium (Se) has received increasing attention in drug modification and property optimization. Herein, we disclose an isothiourea-mediated dynamic kinetic resolution and ester exchange of α-arylselenocarboxylic acids, affording the target molecules with up to 95

Bacterial plant diseases severely threaten agricultural production, necessitating the development of novel and eco-friendly antimicrobial agents. In this study, two thiadiazole metal complexes were rationally designed using a molecular hybridization strategy. Compound T8 displayed outstanding antibacterial activity against Xanthomonas oryzae pv oryzae (Xoo), X. oryzae pv oryzicola (Xoc), and Xanthomonas axonopodis pv citri (Xac) in vitro and in vivo. T8 disrupted bacterial cell wall integrity and enhanced rice defense enzyme activities, effectively inhibiting Xoo proliferation. Integrated proteomic and transcriptomic analyses demonstrated that T8 promoted host mitochondrial respiration and ATP production. Functional experiments revealed that T8 activated the oxidative phosphorylation pathway by enhancing cytochrome c oxidase subunit 6b-1 (COX6b-1) activity. Molecular docking, molecular dynamics simulations, and gene expression analyses further confirmed COX6b-1 as a key mediator. These findings elucidate the molecular basis of T8-induced Xoo resistance and support the development of COX6b-1-protein bactericides.

This study investigated the antiviral activity and molecular mechanisms of oligochitosan against potato virus Y (PVY) in Nicotiana benthamiana. The results demonstrate that oligochitosan exhibits significant anti-PVY activity, achieving a preventive efficacy of 54.7%. Biochemical analyses revealed that oligochitosan treatment enhances the activities of defense-related enzymes and stimulates hydrogen peroxide accumulation in N. benthamiana. Integrated transcriptomic and proteomic analyses identified key differentially expressed genes associated with reactive oxygen species signaling and the mitogen-activated protein kinase pathway, including PYL1, PP2C, OXI1, NDPK4, MAPKKK21 and POD4. Functional characterization demonstrated that oligochitosan specifically upregulates OXI1 expression while enhancing MAPKKK21 and NDPK4 transcript levels, thereby conferring enhanced PVY resistance. These findings establish that oligochitosan-induced plant defense against PVY operates primarily through ROS-mediated activation of the mitogen-activated protein kinase signaling cascade. This work provides novel insights into the molecular basis of the antiviral activity of oligochitosan in plant protection.

BACKGROUND:Plant viruses rely on long-distance transport to establish systemic infection within hosts, and cell-to-cell movement is often a prerequisite for vascular entry and subsequent systemic spread. Therefore, interference with virus movement represents an attractive antiviral strategy. Here, we report a series of perillaldehyde-derived compounds bearing an α-aminophosphonate moiety, evaluate their anti-phytoviral activities, and elucidate the mechanism of a representative lead. RESULTS:A total of 38 target derivatives were designed and synthesized by introducing an aminophosphonate pharmacophore onto the perillaldehyde scaffold. Using the half-leaf lesion assay, compound Y14 was identified as a potent inhibitor against Potato virus Y (PVY), exhibiting an inactivation half-maximal effective concentration (EC50) of 122.40 ± 9.34 μg mL-1, outperforming the commercial antiviral dufulin (140.40 ± 6.75 μg mL-1) and ribavirin (238.90 ± 10.58 μg mL-1). Activity-based protein profiling, molecular docking, microscale thermophoresis, together with immunoblotting and real-time quantitative polymerase chain reaction (RT-qPCR) analyses, collectively suggested that Ser207 in the PVY coat protein (CP) is a key residue for compound Y14 engagement. Notably, the CPS207A mutation markedly reduced the binding affinity of compound Y14 and attenuated PVY systemic infection in planta. Confocal imaging showed that the CPS207A recombinant PVY produced predominantly single-cell fluorescence, indicating impaired cell-to-cell movement. The co-immunoprecipitation results further suggested that this inhibition may arise from disrupted interaction with the host factor NtCPIP. CONCLUSION:This study identifies compound Y14 as an antiviral lead that targets PVY CP and functionally compromises viral intercellular spread, thereby suppressing systemic infection. These findings provide a mechanistically distinctive chemical for PVY management. © 2026 Society of Chemical Industry.

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is a hot spot in the research of green herbicide targets and is often used to prepare novel and efficient herbicides. In this work, we integrated the antiviral disulfide acetal moiety into a pyrimidinedione scaffold, leading to the design and synthesis of a series of novel pyrimidinedione derivatives. The results of the postemergence herbicidal activity assay showed that the majority of the synthesized compounds exhibited significant herbicidal efficacy. Notably, compound S1 controls over 80% of various weeds at only 4.7 g a.i./ha. Further PPO activity experiments showed that compound S1 (IC50 = 0.0151 μM) demonstrated superior PPO inhibition over the reference drug saflufenacil (IC50 = 0.0181 μM). Additionally, at a dose of 150 g a.i./ha, compound S1 is safe for both rice and wheat. Therefore, S1 can be considered a lead for the development of efficient and safe PPO inhibitors.

Piercing-sucking pests cause significant agricultural losses, and widespread neonicotinoid use has led to resistance and ecological concerns. Mesoionic compounds show broad-spectrum insecticidal activity with low cross-resistance, yet the mechanism and potential of tetrahydrothiazolo[3,2-a]pyrimidine mesoionic scaffolds against these pests remain largely unexplored. Here, a series of novel tetrahydrothiazolo[3,2-a]pyrimidine mesoionics containing a benzoxacycle moiety were designed, synthesized, and evaluated for insecticidal activity against Megoura crassicauda (M. crassicauda) and Sogatella furcifera (S. furcifera). All compounds showed notable bioactivity, with H1 displaying the highest aphicidal potency (LC50 = 1.08 mg/L) and its enantiomer (R)-H1 exhibiting markedly enhanced activity (LC50 = 0.31 mg/L), superior to triflumezopyrim (TFM, LC50 = 2.13 mg/L) and comparable to fenmezoditiaz (LC50 = 0.16 mg/L). Acute contact toxicity assays demonstrated that (R)-H1 was substantially less toxic to honeybees (LD50 = 4.58 μg/bee) than TFM (LD50 = 0.55 μg/bee) and fenmezoditiaz (LD50 = 1.28 μg/bee). Mode of action studies, including enzyme activity assays and ELISA, suggest that (R)-H1 interferes with the neural function of aphids. DFT calculations and molecular docking further support the stable, stereoselective binding of (R)-H1 to AChBP, providing a molecular basis for the observed enantioselective activity. Collectively, these findings highlight (R)-H1 as a promising lead for developing environmentally benign insecticides targeting piercing-sucking pests.

As the most fundamental organic unit, the methyl group is ubiquitously present yet frequently overlooked in various insecticide architectures. Despite its simplicity, this moiety plays a pivotal role in insecticide discovery. This perspective highlights documented cases of popular insecticides in which methyl substitution increases target affinity and bioactivity, alongside an analysis of the underlying molecular mechanisms. We propose insights into currently unsolved issues and future directions for leveraging methyl incorporation to accelerate the discovery of new agrochemicals. To our knowledge, this constitutes the first comprehensive perspective on the functional significance of methyl groups in agricultural chemistry. We expect this work to inspire methyl-driven optimization strategies for next-generation insecticides, thereby contributing to sustainable pest management.

Efficient viral proliferation within the host is a critical step in pathogenicity and requires adenosine triphosphate (ATP). The replication, movement and immune evasion of many plant viruses within their hosts are associated with phase separation (PS)-derived aggregates formed by viral components. However, the host factors that drive the formation of these condensates remain largely unknown. This study provides evidence that the nucleocapsid protein (N) of tomato spotted wilt virus (TSWV) recruits the host factor phosphoglycerate kinase (NbPGK) from Nicotiana benthamiana to form phase-separated condensates. This remodels the host glycolytic pathway to generate ATP, supplying energy for viral replication via ribonucleoprotein complexes and acting as a promoter to regulate the PS network, thereby facilitating condensate formation. Notably, we have developed a small-molecule PS modulator, F10. By combining drug affinity-responsive target stability, molecular docking, microscale thermophoresis and bio-layer interferometry techniques allowed F10, we confirmed binding to sites Arg94, Lys192 and Gly228 on TSWV N, residues critical for maintaining NbPGK recruitment. F10 interacts with N, liberating the hijacked host factor NbPGK, and exhibits potent antiviral activity, outperforming the commercial virucide Ningnanmycin. This study elucidates the molecular machinery underlying viral exploitation of host cellular metabolism and identifies a lead compound that is amenable to managing TSWV by targeting this process.

Coumarins are widely distributed natural products with diverse biological activities. In this study, 54 novel coumarin derivatives bearing benzyl chloride and dithioacetal moieties were designed, synthesized, and evaluated for antiviral activity against cucumber mosaic virus (CMV). Several compounds exhibited superior efficacy compared to the commercial agent ningnanmycin. Notably, compound E27 showed the strongest in vivo protective activity, outperforming both ningnanmycin and chitosan oligosaccharide (COS). Mechanistic studies revealed that E27 enhanced defense-related enzyme activities, increased chlorophyll accumulation, and mitigated CMV-induced photosynthetic damage. Transcriptomic analysis demonstrated that E27 significantly upregulated photosynthesis-related pathways, with chlorophyll a/b-binding protein (CAB) identified as a key responsive gene. Functional assays confirmed that CAB silencing reduced host resistance, whereas CAB overexpression suppressed CMV proliferation. In addition, in silico ADME analysis indicated favorable pharmacokinetic properties and low ecological risk. These results highlight E27 as a promising lead for eco-friendly antiviral agrochemical development.

The selectivity of pesticides for harmful insects versus beneficial organisms has long been a critical issue in agriculture. Pyrido-[1,2-a] pyrimidine mesoionics have been widely demonstrated to effectively control a diverse range of insect pests. However, many of their analogues have exhibited high toxicity to bees. Herein, we report a new analogue of pyrido-[1,2-a] pyrimidines designed through oxime ester functionalization. Biological activity tests revealed that these derivatives possess potential aphidicidal activity. Compound WZ18 demonstrates a median lethal concentration (LC50) of 1.73 μg/mL, slightly lower than that of the positive control triflumezopyrim (TFM) (LC50 = 3.05 μg/mL). Notably, WZ18 shows significantly reduced toxicity in acute contact experiments on honey bees (Apis mellifera Ligustica Spinola). Its median lethal dose (LD50) is 6.25 μg a.i./bee, compared to 0.06 μg a.i./bee for TFM. Investigations into the penetration mechanism indicate that the insecticidal activity of WZ18 is primarily due to its systemic property. Moreover, proteomic analyses suggest that WZ18 may interfere with the nervous system of pests. Molecular docking and molecular dynamics simulations further support that WZ18 likely shares a similar mechanism of action with TFM. This study provides a valuable foundation for the development of mesoionic insecticides that are safer for nontarget organisms.

Lasiodiplodia theobromae can cause severe diseases, including leaf spot, leaf necrosis and stem canker in tea plants, leading to substantial losses in both tea leaf production and quality. However, the mechanisms underlying host resistance remain poorly understood. In this study, we identified CsWRKY57 as a nucleus-localised transcription factor whose expression dynamically responds to L. theobromae infection. Transient overexpression and antisense oligonucleotide (AsODN)-mediated silencing in tea leaves, along with stable overexpression in transgenic Nicotiana benthamiana leaves, demonstrated that CsWRKY57 enhanced resistance to L. theobromae. Yeast two-hybrid and bimolecular fluorescence complementation assays revealed that CsWRKY57 interacts with CsTIFY5A in the nucleus, further confirming that CsTIFY5A negatively regulates disease resistance through transient overexpression and AsODN-mediated silencing in tea leaves. DNA affinity purification sequencing, electrophoretic mobility shift assay and dual-luciferase assay indicated that CsWRKY57 binds to the AGTCAA motif in the CsLRR-RLK promoter, thereby activating its expression. Transient overexpression and AsODN-mediated silencing assays in tea leaves demonstrated that CsLRR-RLK positively regulates resistance to L. theobromae. Additionally, degradome sequencing, β-glucuronidase and dual-luciferase assays revealed that miR5368-p5 cleaves CsWRKY57 mRNA. Transient overexpression and AsODN assays in tea leaves, as well as stable overexpression of miR5368-p5 in transgenic N. benthamiana, indicated that miR5368-p5 negatively regulates resistance to L. theobromae. Our results suggest that the miR5368-p5-CsWRKY57-CsLRR-RLK module, which also includes CsTIFY5A interacting with CsWRKY57, plays a critical role in regulating the defence response of tea plants to L. theobromae. The results provide valuable insights into the mechanisms governing the response of tea plants to L. theobromae infection.

BACKGROUND:Sogatella furcifera, commonly known as white-backed planthopper, is a highly threatening migratory pest that feeds on rice and can transmit phytoviruses. Recently, mesoionic insecticides, exemplified by triflumezopyrim (TFM), have proven effective in managing such pests. Nevertheless, available data indicate that TFM remains highly toxic to ecologically important pollinators. Herein, the development of a class of pyrido[1,2-a]pyrimidine-based cinnamic acid analogs, their insecticidal activity, modes of action, and toxicity to bees are disclosed. RESULTS:A total of 37 novel pyrido[1,2-a]pyrimidine mesoionics (W1-W37) incorporating cinnamic amides were systematically designed, synthesized and evaluated for their insecticidal performance. Compound W19 was found to be the most potent, achieving 100% mortality in S. furcifera at both concentrations of 100.00 μg mL-1 and 10.00 μg mL-1, with a median lethal concentration (LC50) of 1.34 μg mL-1. Notably, despite having a slightly higher LC50 value than the positive control TFM (LC50 = 0.21 μg mL-1), W19 exhibited significantly lower acute exposure toxicity (LD50 = 62.37 μg a.i./bee) to Apis mellifera in comparison to TFM (LD50 = 0.51 μg a.i./bee). Employing a combination of proteomics, enzyme activity testing, quantitative real-time PCR and molecular docking technologies, it is proposed that W19 functions as a modulator of nicotinic acetylcholine receptor (nAChR). The reduced risk to honeybees is likely attributed to W19's weaker and less frequent binding to bee nAChR. CONCLUSION:Our study shows that leveraging cinnamic acid derivatives into the design of mesoionic insecticides is expected to lead to the discovery of more selective agrochemicals and improve their compatibility with nontarget organisms. © 2025 Society of Chemical Industry.

As a biological macromolecule, the coat protein (CP) of potato virus Y (PVY) mediates the virus' primary pathogenic behaviors. It has been gradually realized that certain residues on the CP are crucial for functions such as virus particle movement and assembly. However, there are few reports of potential drugs successfully targeting these key residues with unique mechanisms of action. Here, we disclose the first new phytovirucide that acts on the key site Arg157 (R157) on the PVY CP. In this investigation, we developed a series of benzo[b] thiophene-based compounds, strategically introducing sulfonamide functionalities to enhance their antiviral performance. Through bio-screening, derivative C54 (EC50 = 69.2 mu g/mL for inactive activity) emerged as notably more effective against PVY than the established antiviral agent ningnanmycin (EC50 = 79.6 mu g/mL). Mechanistic studies revealed that C54 is an inhibitor of viral particle assembly by specifically binding to the CP residue R 157 , thereby disrupting its interaction with RNA. These results underscore the promise of C54 as a potent antiviral lead and provide a fresh perspective on the strategic design of inhibitors focusing on viral assembly processes.