ABSTRACT
Resistant weeds severely threaten crop yields as they compete with crops for resources required for survival. Trifludimoxazin, a protoporphyrinogen IX oxidase (PPO) inhibitor, can effectively control resistant weeds. However, its crop safety record is unsatisfactory. Consequently, a scaffold-hopping strategy is employed in this study to develop a series of new triazinone derivatives featuring an amide structure. Most compounds depicted excellent herbicidal activity across a broad spectrum at 37.5-150 g ai/ha, among which (R)-I-5 was equivalent to flumioxazin. (R)-I-5 demonstrated significant crop tolerance to rice and wheat, even at 150 g ai/ha. (R)-I-5 exhibited superior pharmacokinetic features compared to flumioxazin and trifludimoxazin. This was depicted by the absorption, distribution, metabolism, excretion, and toxicity predictions. Notably, proteomics-based analysis was applied for the first time to investigate variations among plant proteins before and after herbicide application, shedding light on the conservative and divergent roles of PPO.
Subject(s)
Amides , Enzyme Inhibitors , Herbicides , Plant Weeds , Proteomics , Protoporphyrinogen Oxidase , Triazines , Protoporphyrinogen Oxidase/antagonists & inhibitors , Protoporphyrinogen Oxidase/metabolism , Protoporphyrinogen Oxidase/chemistry , Herbicides/chemistry , Herbicides/pharmacology , Herbicides/chemical synthesis , Plant Weeds/drug effects , Triazines/chemistry , Triazines/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemical synthesis , Amides/chemistry , Amides/pharmacology , Plant Proteins/chemistry , Plant Proteins/antagonists & inhibitors , Plant Proteins/metabolism , Drug Design , Structure-Activity Relationship , Triticum/chemistry , Oryza/chemistry , Oryza/metabolism , Molecular StructureABSTRACT
Bacterial diseases pose a significant threat to the sustainable production of crops. Given the unsatisfactory performance and poor eco-compatibility of conventional bactericides, here we present a series of newly structured bactericides that are inspiringly designed by aurone found in plants of the Asteraceae family. These aurone-derived compounds contain piperazine sulfonamide motifs and have shown promising in vitro performance against Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicola and Xanthomonas axonopodis pv. citri, in particular, compound II23 achieved minimum half-maximal effective concentrations of 1.06, 0.89, and 1.78 µg/mL, respectively. In vivo experiments conducted in a greenhouse environment further revealed that II23 offers substantial protective and curative effects ranging between 68.93 and 70.29% for rice bacterial leaf streak and 53.17-64.43% for citrus bacterial canker, which stands in activity compared with lead compound aurone and commercial thiodiazole copper. Additional physiological and biochemical analyses, coupled with transcriptomics, have verified that II23 enhances defense enzyme activities and chlorophyll levels in rice. Significantly, it also stimulates the accumulation of abscisic acid (ABA) and upregulates the expression of key genes OsPYL/RCAR5, OsBIPP2C1, and OsABF1, thereby activating the ABA signaling pathway in rice plants under biological stress from bacterial infections.
Subject(s)
Piperazines , Plant Diseases , Sulfonamides , Xanthomonas , Plant Diseases/microbiology , Plant Diseases/prevention & control , Xanthomonas/drug effects , Piperazines/pharmacology , Piperazines/chemistry , Sulfonamides/pharmacology , Oryza/microbiology , Anti-Bacterial Agents/pharmacology , Xanthomonas axonopodis/drug effects , BenzofuransABSTRACT
Research on mesoionic structures in pesticide design has gained significant attention in recent years. However, the 1-position of pyridino[1,2-a]pyrimidine is usually designed with 2-chlorothiazole, 2-chloropyridine, or cyano moieties commonly found in neonicotinoid insecticides. In order to enrich the available pharmacophore library, here, we disclose a series of new pyridino[1,2-a]pyrimidine mesoionics bearing indole-containing substituents at the 1-position. Most of these target compounds are confirmed to have good insecticidal activity against aphids through bioevaluation. In addition, a three-dimensional structure-activity relationship model is established to allow access to optimal compound F45 with an LC50 value of 2.97 mg/L. This value is comparable to the property achieved by the positive control triflumezopyrim (LC50 = 2.94 mg/L). Proteomics and molecular docking analysis suggest that compound F45 has the potential to modulate the functioning of the aphid nervous system through its interaction with neuronal nicotinic acetylcholine receptors. This study expands the existing pharmacophore library for the future development of new mesoionic insecticides based on 1-position modifications of the pyridino[1,2-a]pyrimidine scaffold.
Subject(s)
Aphids , Drug Design , Indoles , Insecticides , Molecular Docking Simulation , Pyrimidines , Insecticides/chemistry , Insecticides/chemical synthesis , Insecticides/pharmacology , Animals , Pyrimidines/chemistry , Pyrimidines/pharmacology , Pyrimidines/chemical synthesis , Aphids/drug effects , Indoles/chemistry , Indoles/pharmacology , Indoles/chemical synthesis , Structure-Activity Relationship , Molecular Structure , Receptors, Nicotinic/metabolism , Receptors, Nicotinic/chemistry , Receptors, Nicotinic/drug effectsABSTRACT
The unsatisfactory effects of conventional bactericides and antimicrobial resistance have increased the challenges in managing plant diseases caused by bacterial pests. Here, we report the successful design and synthesis of benzofuran derivatives using benzofuran as the core skeleton and splicing the disulfide moieties commonly seen in natural substances with antibacterial properties. Most of our developed benzofurans displayed remarkable antibacterial activities to frequently encountered pathogens, including Xanthomonas oryzae pv oryzae (Xoo), Xanthomonas oryzae pv oryzicola (Xoc), and Xanthomonas axonopodis pv citri (Xac). With the assistance of the three-dimensional quantitative constitutive relationship (3D-QSAR) model, the optimal compound V40 was obtained, which has better in vitro antibacterial activity with EC50 values of 0.28, 0.56, and 10.43 µg/mL against Xoo, Xoc, and Xac, respectively, than those of positive control, TC (66.41, 78.49, and 120.36 µg/mL) and allicin (8.40, 28.22, and 88.04 µg/mL). Combining the results of proteomic analysis and enzyme activity assay allows the antibacterial mechanism of V40 to be preliminarily revealed, suggesting its potential as a versatile bactericide in combating bacterial pests in the future.
Subject(s)
Anti-Bacterial Agents , Benzofurans , Disulfides , Drug Design , Microbial Sensitivity Tests , Xanthomonas , Benzofurans/pharmacology , Benzofurans/chemistry , Benzofurans/chemical synthesis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Xanthomonas/drug effects , Disulfides/chemistry , Disulfides/pharmacology , Plant Diseases/microbiology , Quantitative Structure-Activity Relationship , Molecular Structure , Xanthomonas axonopodis/drug effects , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Oryza/microbiology , Oryza/chemistryABSTRACT
The control of potato virus Y (PVY) induced crop failure is a challengeable issue in agricultural chemistry. Although many anti-PVY agents are designed to focus on the functionally important coat protein (CP) of virus, how these drugs act on CP to inactivate viral pathogenicity, remains largely unknown. Herein, a PVY CP inhibitor -3j (S) is disclosed, which is accessed by developing unusually efficient (up to 99% yield) and chemo-selective (> 99:1 er in most cases) carbene-catalyzed [3+4] cycloaddition reactions. Compound -3j bears a unique arylimidazole-fused diazepine skeleton and shows chirality-preferred performance against PVY. In addition, -3j (S) as a mediator allows ARG191 (R191) of CP to be identified as a key amino acid site responsible for intercellular movement of virions. R191 is further demonstrated to be critical for the interaction between PVY CP and the plant functional protein NtCPIP, enabling virions to cross plasmodesmata. This key step can be significantly inhibited through bonding with the -3j (S) to further impair pathogenic behaviors involving systemic infection and particle assembly. The study reveals the in-depth mechanism of action of antiviral agents targeting PVY CP, and contributes to new drug structures and synthetic strategies for PVY management.
Subject(s)
Antiviral Agents , Cycloaddition Reaction , Imidazoles , Antiviral Agents/pharmacology , Imidazoles/pharmacology , Imidazoles/chemistry , Potyvirus/drug effects , Catalysis , Capsid Proteins/metabolism , Capsid Proteins/genetics , Plant Diseases/virology , Methane/analogs & derivatives , Methane/pharmacology , Capsid/drug effects , Capsid/metabolismABSTRACT
1,3,4-Oxadiazole thioethers have shown exciting antibacterial activities; however, the current mechanism of action involving such substances against bacteria is limited to proteomics-mediated protein pathways and differentially expressed gene analysis. Herein, we report a series of novel 1,3,4-oxadiazole thioethers containing a carboxamide/amine moiety, most of which show good in vitro and in vivo bacteriostatic activities. Compounds A10 and A18 were screened through CoMFA models as optimums against Xanthomonas oryzae pv. oryzae (Xoo, EC50 values of 5.32 and 4.63 mg/L, respectively) and Xanthomonas oryzae pv. oryzicola (Xoc, EC50 values of 7.58 and 7.65 mg/L, respectively). Compound A10 was implemented in proteomic techniques and activity-based protein profiling (ABPP) analysis to elucidate the antibacterial mechanism and biochemical targets. The results indicate that A10 disrupts the growth and pathogenicity of Xoc by interfering with pathways associated with bacterial virulence, including the two-component regulation system, flagellar assembly, bacterial secretion system, quorum sensing, ABC transporters, and bacterial chemotaxis. Specifically, the translational regulator (CsrA) and the virulence regulator (Xoc3530) are two effective target proteins of A10. Knocking out the CsrA or Xoc3530 gene in Xoc results in a significant reduction in the motility and pathogenicity of the mutant strains. This study contributes available molecular entities, effective targets, and mechanism basis for the management of rice bacterial diseases.
Subject(s)
Oryza , Oxadiazoles , Xanthomonas , Sulfides/chemistry , Proteomics , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Oryza/microbiology , Plant Diseases/microbiologyABSTRACT
The prevention and control of rice bacterial leaf blight (BLB) disease has not yet been achieved due to the lack of effective agrochemicals and available targets. Herein, we develop a series of novel bissulfones and a novel target with a unique mechanism to address this challenge. The developed bissulfones can control Xanthomonas oryzae pv. oryzae (Xoo), and 2-(bis(methylsulfonyl)methylene)-N-(4-chlorophenyl) hydrazine-1-carboxamide (B7) is more effective than the commercial drugs thiodiazole copper (TC) and bismerthiazol (BT). Pyruvate kinase (PYK) in Xoo has been identified for the first time as the target protein of our bissulfone B7. PYK modulates bacterial virulence via a CRP-like protein (Clp)/two-component system regulatory protein (regR) axis. The elucidation of this pathway facilitates the use of B7 to reduce PYK expression at the transcriptional level, block PYK activity at the protein level, and impair the interaction within the PYK-Clp-regR complex via competitive inhibition, thereby attenuating bacterial biology and pathogenicity. This study offers insights into the molecular and mechanistic aspects underlying anti-Xoo strategies that target PYK. We believe that these valuable discoveries will be used for bacterial disease control in the future.
Subject(s)
Oryza , Xanthomonas , Virulence , Pyruvate Kinase/metabolism , Pyruvate Kinase/pharmacology , Anti-Bacterial Agents/metabolism , Oryza/microbiology , Biology , Plant Diseases/prevention & control , Plant Diseases/microbiologyABSTRACT
Pesticides protect crops against pests, and green pesticides are referred to as effective, safe, and eco-friendly pesticides that are sustainably synthesized and manufactured (i.e., green chemistry production). Owing to their high efficacy, safety, and ecological compatibility, green pesticides have become a main direction of global pesticide research and development (R&D). Green pesticides attract attention because of their close association with the quality and safety of agricultural produce. In this review, we briefly define green pesticides and outline their significance, current registration, commercialization, and applications in China, the European Union, and the United States. Subsequently, we engage in an in-depth analysis of the impact of newly launched green pesticides on the environment and ecosystems. Finally, we focus on the potential risks of dietary exposure to green pesticides and the possible hazards of chronic toxicity and carcinogenicity. The status of and perspective on green pesticides can hopefully inspire green pesticide R&D and applications to ensure agricultural production and safeguard human and ecological health.
Subject(s)
Food Security , Pesticides , Humans , Agriculture , Green Chemistry Technology , Crops, Agricultural , China , United StatesABSTRACT
Potato virus Y (PVY) is a highly destructive pathogen that infects Solanum tuberosumvL., commonly known as potato, a crop that produces one of the most crucial food staples of the world. The PVY viral infection can considerably reduce the yield and quality of potatoes, thereby causing significant economic ramifications. Given the unsatisfactory performance of commercially available antiviral agents against PVY, we synthesized a series of novel indole-derived compounds followed by their bioevaluation and investigation of the mechanisms governing their anti-PVY activity. These indole-based derivatives contain dithioacetal as a key chemical moiety, and most of them exhibit promising anti-PVY activities. In particular, compound B2 displays remarkable in vivo protective and inactivating properties, with half-maximal effective concentration (EC50) values of 209.3 and 113.0 µg/mL, respectively, in stark contrast to commercial agents such as ningnanmycin (EC50 = 281.4 and 136.3 µg/mL, respectively) and ribavirin (EC50 = 744.8 and 655.4 µg/mL, respectively). The mechanism using which B2 enhances plant immune response to protect plants from PVY is elucidated using enzyme activity tests, real-time quantitative polymerase chain reaction (RT-qPCR), and proteomics techniques. This study aims to pave the way for developing candidate pesticides and related molecules using antiphytoviral activity.
Subject(s)
Potyvirus , Solanum tuberosum , Indoles/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Ribavirin/pharmacology , Plant Diseases/prevention & controlABSTRACT
Bean aphid (Aphis craccivora) resistance to commonly used insecticides has made controlling these pests increasingly difficult. In this study, we introduced isoxazole and isoxazoline, which possess insecticidal activity, into pyrido[1,2-a]pyrimidinone through a scaffold hopping strategy. We designed and synthesized a series of novel mesoionic compounds that exhibited a range of insecticidal activities against A. craccivora. The LC50 values of compounds E1 and E2 were 0.73 and 0.88 µg/mL, respectively, better than triflumezopyrim (LC50 = 2.43 µg/mL). Proteomics and molecular docking analyses showed that E1 might influence the A. craccivora nervous system by interacting with neuronal nicotinic acetylcholine receptors (nAChRs). This research offers a new approach to the advancement of novel mesoionic insecticides.
Subject(s)
Insecticides , Pyrimidinones , Pyrimidinones/chemical synthesis , Pyrimidinones/chemistry , Pyrimidinones/pharmacology , Insecticides/chemical synthesis , Insecticides/chemistry , Insecticides/pharmacology , Isoxazoles/chemistry , Molecular Structure , Proteomics , Aphids , Animals , Structure-Activity RelationshipABSTRACT
Developing innovative and effective herbicides is of utmost importance since weed management has become a worldwide agricultural production concern, resulting in severe economic losses every year. In this study, a series of new pyrimidinedione compounds were developed via combination of pyrimidinediones with N-phenylacetamide moiety. The herbicidal activity test (37.5-150 g of ai/ha) indicated that most of the new derivatives exhibited excellent herbicidal activity against dicotyledonous weeds, but less against grasses. Among them, compound 34 was identified as the best postemergence herbicidal activities against six species of weeds (Amaranthus retrof lexus, AR; Abutilon theophrasti, AT; Veronica polita, VP; Echinochloa crusgalli, EC; Digitaria sanguinalis, DS; Setaria viridis, SV), which were comparable to the commercial control agent saflufenacil (≥90%). The protoporphyrinogen oxidase (PPO; EC. 1.3.3.4) activity experiment suggested that compound 34 could significantly reduce the PPO content in weeds, the relative expression levels of the PPO gene were verified by real-time quantitative polymerase chain reaction (RT-qPCR), and the results were consistent with the trend of the enzyme activity data. Molecular docking showed that compound 34 could occupy the PPO enzyme catalytic substrate pocket, which played an excellent inhibitory effect on the activity of receptor protein. Meanwhile, the tolerance of compound 34 to cotton was better than that of the commercial agent saflufenacil at 150 g of ai/ha. Thus, compound 34 exhibits the potential to be a new PPO herbicide for weed control in cotton fields. This study provided a basis for the subsequent structural modification and mechanism research of pyrimidinedione derivatives.
Subject(s)
Herbicides , Molecular Docking Simulation , Herbicides/chemistry , Pyrimidinones/pharmacology , Sulfonamides/pharmacology , Plant Weeds , Gossypium/genetics , Structure-Activity RelationshipABSTRACT
In this study, a commercial agent with antivirus activity and moroxydine hydrochloride were employed to perform a lead optimization. A series of 1,3,5-triazine derivatives with piperazine structures were devised and synthesized, and an evaluation of their anti-potato virus Y (PVY) activity revealed that several of the target compounds possessed potent anti-PVY activity. The synthesis of compound C35 was directed by a 3D-quantitative structure-activity relationship that used the compound's structural parameters. The assessment of the anti-PVY activity of compound C35 revealed that its curative, protective, and inactivation activities (53.3 ± 2.5%, 56.9 ± 1.5%, and 85.8 ± 4.4%, respectively) were comparable to the positive control of ningnanmycin (49.1 ± 2.4%, 50.7 ± 4.1%, and 82.3 ± 6.4%) and were superior to moroxydine hydrochloride (36.7 ± 2.7%, 31.4 ± 2.0%, and 57.1 ± 1.8%). In addition, molecular docking demonstrated that C35 can form hydrogen bonds with glutamic acid at position 150 (GLU 150) of PVY CP, providing a partial theoretical basis for the antiviral activity of the target compounds.
Subject(s)
Potyvirus , Tobacco Mosaic Virus , Piperazine , Molecular Docking Simulation , Antiviral Agents/chemistry , Triazines/pharmacologyABSTRACT
Twenty-eight imidazo[1,2-c]pyrimidin-5(6H)-one nucleoside derivatives incorporating a sulfonamide scaffold with preferable inactivating activities on pepper mild mottle virus (PMMoV) were designed and synthesized. Then, compound B29 with illustrious inactivating activity against PMMoV was received on the basis of the three-dimensional quantitative structure-activity relationship (3D-QSAR) model, with the EC50 of 11.4 µg/mL, which was superior to ningnanmycin (65.8 µg/mL) and template molecule B16 (15.3 µg/mL). Furthermore, (1) transmission electron microscopy (TEM) indicated that B29 could cause severe fracture of virions; (2) microscale thermophoresis (MST) and molecular docking further demonstrated that B29 had faintish binding affinities with PMMoV CPR62A (Kd = 202.84 µM), PMMoV CPL144A (Kd = 141.57 µM), and PMMoV CPR62A,L144A (Kd = 332.06 µM) compared to PMMoV CP (Kd = 4.76 µM); and (3) western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results of pCB-GFP-PMMoV CPR62A, pCB-GFP-PMMoV CPL144A, and pCB-GFP-PMMoV CPR62A,L144A were consistent with MST and confocal. In brief, the above results indicated that the amino acids at positions 62 and 144 of PMMoV CP might be the key amino acid sites of B29 acted on.
Subject(s)
Nucleosides , Tobamovirus , Molecular Docking Simulation , Amino Acids , SulfanilamideABSTRACT
With the continuous evolution of insect resistance, it is a tremendous challenge to control the fall armyworm (Spodoptera frugiperda) with traditional insecticides. To solve this pending issue, a series of novel isoxazoline derivatives containing diaryl ether structures were designed and synthesized, and most of the target compounds exhibited excellent insecticidal activity. Based on the three-dimensional quantitative structure-activity relationship (3D-QSAR) model analysis, we further optimized the molecular structure with compound L35 obtained and tested for its activity. Compound L35 (LC50 = 1.69 mg/L) exhibited excellent insecticidal activity against S. frugiperda, which was better than those of commercial fipronil (LC50 = 70.78 mg/L) and indoxacarb (LC50 = 5.37 mg/L). The enzyme-linked immunosorbent assay showed that L35 could upregulate the levels of GABA in insects. In addition, molecular docking and transcriptomic results also indicated that compound L35 may affect the nervous system of S. frugiperda by acting on GABA receptors. Notably, through high-performance liquid chromatography (HPLC), we were able to obtain the two enantiomers of compound L35, and the insecticidal activity test revealed that S-(+)-L35 was 44 times more active than R-(-)-L35 against S. frugiperda. This study established the chemistry basis and mechanistic foundations for the future development of pesticide candidates against fall armyworms.
Subject(s)
Ether , Insecticides , Animals , Spodoptera , Molecular Docking Simulation , Insecticides/pharmacology , Insecticides/chemistry , Ethyl Ethers , Ethers , LarvaABSTRACT
Isoxazoline structures are widely found in natural products and are rich in biological activities. This study discloses the development of a series of novel isoxazoline derivatives by introducing acylthiourea fragments to access insecticidal activity. All synthetic compounds were examined for their insecticidal activity against Plutella xylostella, with results showing moderate to strong activity. Based on this, the structure-activity relationship analysis was carried out via the constructed three-dimensional quantitative structure-activity relationship model to further guide the structure optimization, resulting in the optimal compound 32. The LC50 of compound 32 against Plutella xylostella was 0.26 mg/L, demonstrating better activity than the positive control, ethiprole (LC50 = 3.81 mg/L), avermectin (LC50 = 12.32 mg/L), and compounds 1-31. The insect GABA enzyme-linked immunosorbent assay demonstrated that compound 32 might act on the insect GABA receptor, and the molecular docking assay further illustrated the mode of action of compound 32 with the GABA receptor. In addition, the proteomics analysis indicated that the action of compound 32 on Plutella xylostella was multi-pathway.
Subject(s)
Insecticides , Moths , Animals , Larva , Insecticides/pharmacology , Insecticides/chemistry , Molecular Docking Simulation , Structure-Activity Relationship , Quantitative Structure-Activity RelationshipABSTRACT
A series of isoxazoline derivatives containing diacylhydrazine moieties were designed and synthesized as potential insecticides. Most of these derivatives exhibited good insecticidal activities against Plutella xylostella, and some compounds exhibited excellent insecticidal activities against Spodoptera frugiperda. Especially, D14 showed outstanding insecticidal activity against P. xylostella (LC50 = 0.37 µg/mL), which was superior to that of ethiprole (LC50 = 2.84 µg/mL) and tebufenozide (LC50 = 15.3 µg/mL) and similar to that of fluxametamide (LC50 = 0.30 µg/mL). Remarkably, the insecticidal activity of D14 against S. frugiperda (LC50 = 1.72 µg/mL) was superior to that of chlorantraniliprole (LC50 = 3.64 µg/mL) and tebufenozide (LC50 = 60.5 µg/mL) but lower than that of fluxametamide (LC50 = 0.14 µg/mL). The results of electrophysiological experiments, molecular docking, and proteomics experiments indicate that compound D14 acts by interfering with the γ-aminobutyric acid receptor to control pests.
Subject(s)
Insecticides , Hydrazines/pharmacology , Insecticides/pharmacology , Molecular Docking Simulation , Receptors, GABA , Isoxazoles/chemistry , Isoxazoles/pharmacologyABSTRACT
Ethylicin (ET) was reported to be promising in the control of rice bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae (Xoo). The detailed mechanism for this process remains unknown. Disclosed here is an in-depth study on the action mode of ET to Xoo. Through plant physiological and biochemical analysis, it was found that ET could inhibit the proliferation of Xoo by increasing the content of defense enzymes and chlorophyll in rice (Oryza sativa ssp. Japonica cv. Nipponbare). Label-free quantitative proteomic analysis showed that ET affected the rice abscisic acid (ABA) signal pathway and made the critical differential calcium-dependent protein kinase 24 (OsCPK24) more active. In addition, the biological function of OsCPK24 as a mediator for rice resistance to Xoo was determined through the anti-Xoo phenotypic test of OsCPK24 transgenic rice and the affinity analysis of the OsCPK24 recombinant protein in vitro and ET. This study revealed the molecular mechanism of ET-induced resistance to Xoo in rice via OsCPK24, which provided a basis for the development of new bactericides based on the OsCPK24 protein.
Subject(s)
Oryza , Xanthomonas , Oryza/metabolism , Proteomics , Abscisic Acid/metabolism , Plant Diseases/microbiologyABSTRACT
3-Hydroxy-2-oxindole motif constitutes a core structure in numerous natural products and imparts notable biological activities. Here, we describe the design and synthesis of four series of novel 3-substituted-3-hydroxy-2-oxindole derivatives containing sulfonamide moiety along with their antiviral activities against potato virus Y (PVY). Compound 10b displayed optimal antiviral activity and superior anti-PVY activity compared with the lead compound and commercial Ningnanmycin in terms of curative and protective effects. Additionally, 10b considerably inhibited PVY systemic infection in Nicotiana benthamiana. Physiological and biochemical analyses revealed that the activities of the four crucial defense-related enzymes increased in the tobacco plant following treatment with 10b. RNA-sequencing analysis revealed that 10b substantially induced the upregulation of 38 differentially expressed genes, which were enriched in the photosynthesis pathway. These findings suggest that 10b is a promising antiviral agrochemical that can effectively control PVY infection and trigger plant host immunity to develop virus resistance. This study provides novel molecular entities and ideas for developing new pesticides.
Subject(s)
Potyvirus , Tobacco Mosaic Virus , Antiviral Agents/chemistry , Oxindoles/pharmacology , Up-Regulation , Sulfonamides/pharmacology , Nicotiana , Plant DiseasesABSTRACT
The development of effective antibacterial agents equipped with novel action modes and unique skeletons starting from natural compounds serves as an important strategy in the modern pesticide industry. Disclosed here are a series of novel indole derivatives containing pyridinium moieties and their antibacterial activity evaluation against two prevalent phytopathogenic bacteria, Xanthomonas oryzae pv. oryzicola (Xoc) and X. oryzae pv. oryzae (Xoo). A three-dimensional (3D)-QSAR model was adopted to discover higher activity like title compounds based on the Xoc antibacterial activity of the tested compounds. Compound 43 was consequently designed, and it displayed higher antibacterial activity as expected with the half-maximal effective concentration EC50 values of 1.0 and 1.9 µg/mL for Xoo and Xoc, respectively, which were better than those of the commercial drug thiodiazole copper (TC) (72.9 and 87.5 µg/mL). Under greenhouse conditions, the results of a rice in vivo pot experiment indicated that the protective and curative activities of compound 43 against rice bacterial leaf streak (BLS) and rice bacterial blight (BLB) were 45.0 and 44.0% and 42.0 and 39.3%, respectively, which were better than those of the commercial agent thiodiazole copper (38.0 and 37.9%, 38.6 and 37.0%) as well. Scanning electron microscopy images, defense enzyme activity tests, and proteomic techniques were utilized in a preliminary mechanism study, suggesting that compound 43 shall modulate and interfere with the physiological processes and functions of pathogenic bacteria.
Subject(s)
Oryza , Pesticides , Xanthomonas , Anti-Bacterial Agents/pharmacology , Copper/pharmacology , Indoles/pharmacology , Microbial Sensitivity Tests , Oryza/microbiology , Oxadiazoles/pharmacology , Pesticides/pharmacology , Plant Diseases/microbiology , Plant Diseases/prevention & control , ProteomicsABSTRACT
BACKGROUND: In our previous work, we applied a new synthetic strategy to design and synthesize a series of imidazopyridine mesoionic derivatives with an ester group. The newly synthesized compounds had excellent insecticidal activity against aphids; however, insecticidal activity against planthoppers was less than satisfactory. In the present study, we designed and synthesized a series of novel imidazopyridine mesoionic compounds, containing an amido group, and these compounds were found to have improved insecticidal activity against planthoppers. RESULTS: The bioassay results demonstrated that most of the target compounds had moderate-to-good insecticidal activity against Sogatella furcifera, and some exhibited good-to-excellent insecticidal activity against Aphis craccivora. Among them, compound C6 had the highest insecticidal activity against S. furcifera and A. craccivora, with LC50 values of 10.5 and 2.09 µg mL-1 , respectively. Proteomic results suggested that the differentially expressed proteins mainly were enriched in the nervous system-related pathways after compound C6 treatment. Enzymatic assay results showed that compound C6 and triflumezopyrim had a certain inhibitory effect on acetylcholinesterase. Molecular docking and real-time quantitative PCR results indicated that compound C6 not only may act on the nicotinic acetylcholine receptor, but also may interact with the α4 and ß1 subunits of this receptor. CONCLUSION: The results reported here contribute to the development of new mesoionic insecticides and further our understanding of the mode-of-action of imidazopyridine mesoionic derivatives. © 2022 Society of Chemical Industry.