Novel trans-Resveratrol Derivatives: Design, Synthesis, Antibacterial Activity, and Mechanisms.

Rice bacterial leaf blight and rice bacterial leaf streak have induced tremendous damage to production of rice worldwide. To discover an effective novel antibacterial agent, a series of novel trans-resveratrol (RSV) derivatives containing 1,3,4-oxadiazole and amide moieties were designed and synthesized for the first time. Most of them showed excellent antibacterial activities against Xanthomonas oryzae pv oryzicola and Xanthomonas oryzae pv oryzae. Especially, compound J12 had the best inhibitory with the half-maximal effective concentration values of 4.2 and 5.0 mg/L, respectively, which were better than that of RSV (63.7 and 75.4 mg/L), bismerthiazol (79.5 and 89.6 mg/L), and thiodiazole copper (105.4 and 112.8 mg/L). Furthermore, compound J12 had an excellent control effect against rice bacterial leaf streak and rice bacterial leaf blight, with protective activities of 46.2 and 42.1% and curative activities of 44.5 and 41.7%, respectively. Preliminary mechanisms indicated that compound J12 could not only remarkably decrease biofilm formation, extracellular polysaccharide production, and the synthesis of extracellular enzymes but also destroy bacterial cell surface morphology, thereby reducing the pathogenicity of bacteria. In addition, compound J12 could increase the activity of defense-related enzymes and affect the expression of multiple pathogenic-related genes including plant-pathogen interaction, the MAPK signaling pathway, and phenylpropanoid biosynthesis, and this could improve the defense of rice against rice bacterial leaf streak infection. The present work indicates that the RSV derivatives can be used as promising candidates for the development of antibacterial agents.

Ferulic Acid Dimers as Potential Antiviral Agents by Inhibiting TMV Self-Assembly.

A series of ferulic acid dimers were designed, synthesized, and evaluated for anti-TMV activity. Biological assays demonstrated that compounds A6, E3, and E5 displayed excellent inactivating against tobacco mosaic virus (TMV) with EC50 values of 62.8, 94.4, and 85.2 µg mL-1, respectively, which were superior to that of ningnanmycin (108.1 µg mL-1). Microscale thermophoresis indicated that compounds A6, E3, and E5 showed strong binding capacity to TMV coat protein with binding affinity values of 1.862, 3.439, and 2.926 µM, respectively. Molecular docking and molecular dynamics simulation revealed that compound A6 could firmly bind to the TMV coat protein through hydrogen and hydrophobic bonds. Transmission electron microscopy and self-assembly experiments indicated that compound A6 obviously destroyed the integrity of the TMV particles and blocked the virus from infecting the host. This study revealed that A6 can be used as a promising leading structure for the development of antiviral agents by inhibiting TMV self-assembly.

Discovery of Novel N-Phenyltriazinone Derivatives Containing Oxime Ether or Oxime Ester Moieties as Promising Protoporphyrinogen IX Oxidase Inhibitors.

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is one of the most important targets for the discovery of green herbicides. In order to find novel PPO inhibitors with a higher herbicidal activity, a series of novel N-phenyltriazinone derivatives containing oxime ether and oxime ester groups were designed and synthesized based on the strategy of pharmacophore and scaffold hopping. Bioassay results revealed that some compounds showed herbicidal activities; especially, compound B16 exhibited broad-spectrum and excellent 100% herbicidal effects to Echinochloa crusgalli, Digitaria sanguinalis, Setaria faberii, Abutilon juncea, Amaranthus retroflexus, and Portulaca oleracea at a concentration of 37.5 g a.i./ha, which were comparable to trifludimoxazin. Nicotiana tabacum PPO (NtPPO) enzyme inhibitory assay indicated that B16 showed an excellent enzyme inhibitory activity with a value of 32.14 nM, which was similar to that of trifludimoxazin (31.33 nM). Meanwhile, compound B16 revealed more safety for crops (rice, maize, wheat, peanut, soybean, and cotton) than trifludimoxazin at a dose of 150 g a.i./ha. Moreover, molecular docking and molecular dynamics simulation further showed that B16 has a very strong and stable binding to NtPPO. It indicated that B16 can be used as a potential PPO inhibitor and herbicide candidate for application in the field.

Synthesis, biological evaluation, and molecular docking of novel ferulic acid derivatives containing a 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine skeleton.

In this study, 24 novel ferulic acid derivatives containing 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine were designed and synthesized. Bioactivity assay showed that some of the target compounds exhibited moderate to good antifungal activity against Botryosphaeria dothidea BD), Phomopsis sp. (PS), Botrytis cinerea (BC), Fusarium spp. (FS), Fusarium graminearum (FG), and Colletotrichum sp. (CS). Especially, compound 6f demonstrated superior antifungal activity against Phomopsis sp., with an EC50 value of 12.64 µg mL-1, outperforming pyrimethanil (35.16 µg mL-1) and hymexazol (27.01 µg mL-1). Meanwhile, compound 6p showed strong antibacterial activity against X. axonopodis pv. citri (XAC) in vitro, with an inhibition ratio of 85.76%, which was higher than thiodiazole copper's 76.59% at 100 µg mL-1. Furthermore, molecular docking simulations elucidated that compound 6f engaged in hydrogen bonding with the succinate dehydrogenase (SDH) enzyme at SER-17, SER-39, ARG-14 and ARG-43 sites, clarifying its mode of action. This study highlights the potential of these novel ferulic acid derivatives as promising agents for controlling fungal and bacterial threats to plant health. To the best of our knowledge, this study represents the first report on the antifungal and antibacterial properties of ferulic acid derivatives containing 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine skeleton.

Discovery of Novel Pyridazine Herbicides Targeting Phytoene Desaturase with Scaffold Hopping.

Phytoene desaturase (PDS) is a critical functional enzyme in blocking ζ-carotene biosynthesis and is one of the bleaching herbicide targets. At present, norflurazon (NRF) is the only commercial pyridazine herbicide targeting PDS. Therefore, developing new and diverse pyridazine herbicides targeting PDS is urgently required. In this study, diflufenican (BF) was used as the lead compound, and a scaffold-hopping strategy was employed to design and synthesize some pyridazine derivatives based on the action mode of BF and PDS. The preemergence herbicidal activity tests revealed that compound 6-chloro-N-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenoxy)pyridazine-4-carboxamide (B1) with 2,4-diF substitution in the benzeneamino ring showed 100% inhibition rates against the roots and stems of Echinochloa crus-galli and Portulaca oleracea at 100 µg/mL, superior to the inhibition rates of BF. Meanwhile, compound B1 demonstrated excellent postemergence herbicidal activity against broadleaf weeds, which was similar to that of BF (inhibition rate of 100%) but superior to that of NRF. This indicated that 6-Cl in the pyridazine ring is the key group for postemergence herbicidal activity. In addition, compound B1 could induce downregulation of PDS gene expression, 15-cis-phytoene accumulation, and Y(II) deficiency and prevent photosynthesis. Therefore, B1 can be considered as a promising candidate for developing high-efficiency PDS inhibitors.

Eco-Friendly Cinnamic Acid Derivatives Containing Glycoside Scaffolds as Potential Antiviral Agents.

Natural products are a crucial source in the development of new eco-friendly antiviral agents to control plant viral diseases. In our previous studies, some ferulic acid derivatives with good antiviral activity were obtained as an immune activator. To continue the discovery of eco-friendly antiviral agents, different monosaccharides were introduced into cinnamic acid skeletons by an activity-based strategy to obtain a series of cinnamic acid derivatives containing glycoside scaffolds, and their antiviral activities against tobacco mosaic virus (TMV) and tomato spotted wilt virus (TSWV) were evaluated. Among them, compound 8d showed the greatest protective activities against TMV and TSWV, with the EC50 values of 128.5 and 236.8 µg mL-1, respectively, which were superior to those of ningnanmycin (238.5 and 315.7 µg mL-1, respectively). Moreover, compound 8d could significantly improve the defense enzyme activities of peroxidase, chitinase, and ß-1,3-glucanase. Proteomic and transcriptome analyses indicated that compound 8d regulated gene transcription and protein expression levels involved in the defense response to resist virus infection. The present study revealed that compound 8d is a potential lead candidate for the development of novel, eco-friendly, and natural-product-based antiviral agents.

Carboxylic Acid Derivatives in Herbicide Development.

Carboxylic acids and their derivatives are extensively found in natural and non-natural compounds with proven bioactivities. They have made great contributions to the development of herbicides and herbicidal lead structures in the past 70 years. Carboxylic acid-related herbicidal molecules have targeted a diversity of biosynthetic pathways, proteins, enzymes, energetic metabolism systems, and other reaction sites through different mechanisms. It is significant and helpful for us to know the herbicidal targets and mechanisms of the carboxylic acid-related herbicides as well as the basic rules for the design and development of herbicidal lead structures. We therefore summarize here the overall development of carboxyl group-containing herbicides and herbicidal molecules in the past 20 years based on their structural properties and herbicidal mechanisms.

Cypyrafluone, a 4-Hydroxyphenylpyruvate Dioxygenase Inhibitor to Control Weed in Wheat Fields.

As a bleaching herbicide, cypyrafluone was applied postemergence in wheat fields for annual weed control; especially, this herbicide possesses high efficacy against cool-season grass weed species such as Alopecurus aequalis and Alopecurus japonicus. In this study, the target of action of cypyrafluone on 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibition was confirmed. This herbicide caused severe foliar whitening symptoms at 5-7 days after treatment (DAT) and death of the whole plant within 10 DAT. Significant increases in phytoene content and significant decreases in kinds of carotenoid and chlorophyll pigments were observed. The content of chlorophyll pigments in cypyrafluone-treated Spirodela polyrhiza decreased upon the addition of homogentisic acid (HGA), which indicated that cypyrafluone prevents the HGA production, possibly by inhibiting the catalytic activity of 4-HPPD. Indeed, cypyrafluone strongly inhibited the catalytic activity of Arabidopsis thaliana HPPD produced by Escherichia coli, which was approximately 2 times less effective than mesotrione. In addition, overexpression of Oryza sativa HPPD in rice and A. thaliana both conferred a high tolerance level to cypyrafluone on them. Molecular docking found that cypyrafluone bonded well to the active site of the HPPD and formed a bidentate coordination interaction with the Fe2+ atom, with distances of 2.6 and 2.7 Å between oxygen atoms and the Fe2+ atom and a binding energy of -8.0 kcal mol-1.

Novel 1-Indanone derivatives containing oxime and oxime ether moieties as immune activator to resist plant virus.

BACKGROUND: Vegetable viruses are difficult to prevent and control in the field, causing massive economic losses of agricultural production in the world. A new natural product-based antiviral agent would be an effective means to control viral diseases. As a class of natural products, 1-indanones present various pharmacologically actives, while their application in agriculture remains to be found. RESULTS: A series of novel 1-indanone derivatives were designed and synthesized and the antiviral activities were systematically evaluated. Bioassays showed that most compounds exhibited good protective activities against cucumber mosaic virus (CMV), tomato spotted wilt virus (TSWV), and pepper mild mottle virus (PMMoV). Notably, compound 27 exhibited the best protective effects against PMMoV with EC50 values of 140.5 mg L-1 , superior to ninanmycin (245.6 mg L-1 ). Compound 27 induced immunity responses through multilayered regulation on mitogen-activated protein kinase, plant hormone signal transduction and phenylpropanoid biosynthesis pathways. CONCLUSION: These 1-indanone derivatives especially compound 27 can be considered as potential immune activators to resist plant virus. © 2023 Society of Chemical Industry.

Discovery of 1,2,4-Oxadiazole Derivatives Containing Haloalkyl as Potential Acetylcholine Receptor Nematicides.

Plant-parasitic nematodes pose a serious threat to crops and cause substantial financial losses due to control difficulties. Tioxazafen (3-phenyl-5-thiophen-2-yl-1,2,4-oxadiazole) is a novel broad-spectrum nematicide developed by the Monsanto Company, which shows good prevention effects on many kinds of nematodes. To discover compounds with high nematocidal activities, 48 derivatives of 1,2,4-oxadiazole were obtained by introducing haloalkyl at the 5-position of tioxazafen, and their nematocidal activities were systematically evaluated. The bioassays revealed that most of 1,2,4-oxadiazole derivatives showed remarkable nematocidal activities against Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Ditylenchus dipsaci. Notably, compound A1 showed excellent nematocidal activity against B. xylophilus with LC50 values of 2.4 µg/mL, which was superior to that of avermectin (335.5 µg/mL), tioxazafen (>300 µg/mL), and fosthiazate (436.9 µg/mL). The transcriptome and enzyme activity results indicate that the nematocidal activity of compound A1 was mainly related to the compound which affected the acetylcholine receptor of B. xylophilus.

Discovery of Novel Pyrazole Derivatives with Improved Crop Safety as 4-Hydroxyphenylpyruvate Dioxygenase-Targeted Herbicides.

As one of the essential herbicide targets, 4-hydroxyphenylpyruvate dioxygenase (HPPD) has recently been typically used to produce potent new herbicides. In continuation with the previous work, several pyrazole derivatives comprising a benzoyl scaffold were designed and synthesized, and their inhibitory effects on Arabidopsis thaliana hydroxyphenylpyruvate dioxygenase (AtHPPD) and herbicidal activities were comprehensively evaluated in this study. Compound Z9 showed top-rank inhibitory activity to AtHPPD with an half-maximal inhibitory concentration (IC50) value of 0.05 µM, which was superior to topramezone (1.33 µM) and mesotrione (1.76 µM). Compound Z21 exhibited superior preemergence inhibitory activity against Echinochloa crusgalli, with stem and root inhibition rates of 44.3 and 69.6%, respectively, compared to topramezone (16.0 and 53.0%) and mesotrione (12.8 and 41.7%). Compounds Z5, Z15, Z20, and Z21 showed excellent postemergence herbicidal activities at a dosage of 150 g ai/ha, along with distinct bleaching symptoms and higher crop safety than topramezone and mesotrione, and they all were safe for maize, cotton, and wheat with injury rates of 0 or 10%. In addition, the molecular docking analysis also revealed that these compounds formed hydrophobic π-π interactions with Phe360 and Phe403 to AtHPPD. This study suggests that pyrazole derivatives containing a benzoyl scaffold could be used as new HPPD inhibitors to develop pre- and postemergence herbicides and be applied to additional crop fields.

Novel Cyclized Derivatives of Ferulic Acid as Potential Antiviral Agents through Activation of Photosynthesis.

To further develop new antiviral agents, several novel cyclized derivatives of ferulic acid were designed and synthesized. Their antiviral activities were evaluated against the cucumber mosaic virus (CMV), pepper mild mottle virus (PMMoV), and tomato spotted wilt virus (TSWV). The results showed that some ferulic acid derivatives exhibited desirable antiviral activities. Particularly, compound 5e exhibited excellent protective activities against CMV, PMMoV, and TSWV, with EC50 values of 167.2, 102.5, and 145.8 µg mL-1, respectively, which were superior to those obtained for trans-ferulic acid (581.7, 611.2, and 615.4 µg mL-1), dufulin (312.6, 302.5, and 298.2 µg mL-1), and ningnanmycin (264.3, 282.5, and 276.5 µg mL-1). Thereafter, the protective mechanisms of 5e were evaluated through photosynthesis evaluation, transcriptome profiling, and proteomic analysis. The results indicated that 5e significantly activated the expression levels of photosynthesis-related regulatory genes and proteins in tobacco plants and promoted the accumulation of defense molecules to resist viral infection. Thus, the findings of this study indicated that novel cyclized ferulic acid derivatives are potential antiviral agents that act via regulating photosynthesis in the host.

Two strains Neocosmosporastercicola (Sordariomycetes, Nectriaceae) with high nematicidal activity, isolated from the cysts of Globodera sp. (Heteroderidae) in China.

Plant-parasitic nematodes (PPNs) are significant pests that result in considerable economic losses in global crop production. Due to the high toxicity of chemical nematicides, there is a need to develop new strategies for nematode control. In this context, nematophagous fungi may offer a viable option for biological control. Two fungal strains (GUCC2212 and GUCC2232) were isolated from cysts of Globodera sp., identified as Neocosmosporastercicola. The fungal filtrates of the strains were evaluated for their nematicidal activity against three species of PPNs: Aphelenchoidesbesseyi, Bursaphelenchusxylophilus and Ditylenchusdestructor. The fermentation filtrates of two strains exhibited substantial toxicity towards the evaluated nematodes, with mortality rates reaching up to 100% within 72 h. Concurrently, N.stercicola also demonstrated predatory and parasitic behavior. The eggs of Globodera sp. were parasitized by the two strains. N.stercicola represents a newly recorded species in China and a novel nematophagous species. In conclusion, the two strains of N.stercicola show promise as biocontrol agents for PPNs management.

Design, Synthesis, and Biological Activity of Novel Chalcone Derivatives Containing an 1,2,4-Oxadiazole Moiety.

To discover a lead compound for agricultural use, 34 novel chalcone derivatives containing an 1,2,4-oxadiazole moiety were designed and synthesized. Their nematocidal activities against Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Ditylenchus dipsaci and their antiviral activities against tobacco mosaic virus (TMV), pepper mild mottle virus (PMMoV), and tomato spotted wilt virus (TSWV) were evaluated. Biological assay results indicate that compounds A13 and A14 showed good nematocidal activities against B. xylophilus, A. besseyi, and D. dipsaci, with LC50 values of 35.5, 44.7, and 30.2 µg/ml and 31.8, 47.4, and 36.5 µg/ml, respectively, which are better than tioxazafen, fosthiazate, and abamectin. Furthermore, compound A16 demonstrated excellent protective activity against TMV, PMMoV, and TSWV, with EC50 values of 210.4, 156.2, and 178.2 µg/ml, respectively, which are superior to ningnanmycin (242.6, 218.4, and 180.5 µg/ml).

Design, synthesis, antiviral activity, and mechanisms of novel ferulic acid derivatives containing amide moiety.

To explore the novel compounds with high antiviral activity, three series ferulic acid derivatives containing amide moiety were gradually designed and synthesized based on antiviral activity tracking. The bioassay results exhibited that some target compounds had notable antiviral activities against tomato spotted wilt virus (TSWV) and cucumber mosaic virus (CMV). Compounds Y1, Y2, Y8, Z1 and Z2 presented splendid curative, protective, and inactivating activities to TSWV and CMV at 500 µg/mL. Especially, these compounds displayed outstanding inactivating effects on TSWV with the EC50 values of 225.9, 126.1, 224.6, 216.1, and 147.3 µg/mL, which were superior to ningnanmycin (249.1 µg/mL) and ribavirin (315.7 µg/mL). Furthermore, the antiviral mechanisms of compound Y2 were investigated by conducting microscale thermophoresis experiment and molecular docking experiment. The results suggested that compound Y2 performed excellent binding affinity to TSWV coat protein (TSWV CP) with the binding constant of 2.14 µM, which due to two strong hydrogen bonds of compound Y2 to the key amino acids ARG94 of TSWV CP. Therefore, compound Y2 can be regarded as a leading structure for development of the potential antiviral agent.

Novel Pyrazole Amides as Potential 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for the development of new herbicides. HPPD inhibitors can hinder photosynthesis and induce weed death with bleaching symptoms. To explore the novel skeleton of HPPD inhibitors, a series of novel pyrazole amide derivatives were synthesized and evaluated for their inhibitory effects on Arabidopsis thaliana HPPD (AtHPPD) and herbicidal activities. Some compounds had excellent inhibitory activities against AtHPPD. Among them, compound B5 displayed top-rank inhibitory activity against AtHPPD with an IC50 value of 0.04 µM, which was obviously superior to that of topramezone (IC50 value of 0.11 µM). Furthermore, compounds B2 and B7 had 100% herbicidal activities in Petri dish assays against Portulaca oleracea and Amaranthus tricolor at 100 µg/mL. In particular, compound B7 not only possessed strong AtHPPD inhibitory activity but also exhibited significant preemergence herbicidal activity. However, compound B7 was completely harmless to soybean, cotton, and wheat. In addition, the molecular docking and microscale thermophoresis measurement experiment verified that compounds can bind well with AtHPPD via π-π interactions. The present work provides a new approach for the rational design of more effective HPPD inhibitors, and pyrazole amides could be used as useful substructures for the development of new HPPD inhibitors and preemergence herbicidal agents.

Polymyxin B1 and E2 From Paenibacillus polymyxa Y-1 for Controlling Rice Bacterial Disease.

To discover novel microbial pesticide for controlling rice bacterial disease, polymyxin B1 and E2 were firstly isolated from the supernatant of fermentation broth of Paenibacillus polymyxa Y-1 by bioactivity tracking separation. It is shown that polymyxin B1 and E2 had remarkable in vitro inhibitory activities to Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc) with the EC50 values of 0.19 µg/ml and 0.21 µg/ml against Xoo, and 0.32 µg/ml and 0.41 µg/ml against Xoc, respectively, which were better than those of Zhongshengmycin (0.31 µg/ml and 0.73 µg/ml) and Bismerthiazol (77.48 µg/ml and 85.30 µg/ml). Polymyxins B1 and E2 had good protection and curative activities against rice bacterial leaf blight (BLB) and rice bacterial leaf streak (BLS) in vivo. The protection and curative activities of polymyxins B1 (45.8 and 35.8%, respectively) and E2 (41.2 and 37.0%, respectively) to BLB were superior to those of Zhongshengmycin (34.8 and 29.8%, respectively) and Bismerthiazol (38.0 and 33.5%, respectively). Meanwhile, the protection and curative activities of polymyxins B1 (44.8 and 39.8%, respectively) and E2 (42.9 and 39.9%, respectively) to BLS were also superior to those of Zhongshengmycin (39.7 and 32.0%, respectively) and Bismerthiazol (41.5 and 34.3%, respectively). Polymyxin B1 exerted the anti-pesticide properties via destroying the cell integrity of Xoo, reducing its infectivity and enhancing rice resistance against pathogens through activating the phenylpropanoid biosynthesis pathway of rice. It is indicated that polymyxin B1 and E2 were potential microbial pesticides for controlling rice bacterial disease.

Active Metabolites From the Endophyte Paenibacillus polymyxa Y-1 of Dendrobium nobile for the Control of Rice Bacterial Diseases.

Microbial bactericides have been a research hotspot in recent years. In order to find new microbial fungicides for preventing and treating rice bacterial diseases, Paenibacillus polymyxa Y-1 (P. polymyxa Y-1) was isolated from Dendrobium nobile in this study, and the optimal medium was selected by a single-factor experiment, and then eight metabolites were isolated from P. polymyxa Y-1 fermentation broth by bioactivity tracking separation. The bioassay results showed that 2,4-di-tert-butylphenol, N-acetyl-5-methoxytryptamine, and P-hydroxybenzoic acid have good antibacterial activity against Xanthomonas oryzae pv. Oryzicola (Xoo) and Xanthomonas oryzae pv. oryzae (Xoc), with 50% effective concentration values of 49.45 µg/ml, 64.22 µg/ml, and 16.32 µg/ml to Xoo, and 34.33 µg/ml, 71.17 µg/ml, and 15.58 µg/ml to Xoc, respectively, compared with zhongshengmycin (0.42 and 0.82 µg/ml, respectively) and bismerthiazol (85.64 and 92.49 µg/ml, respectively). In vivo experiments found that 2,4-di-tert-butylphenol (35.9 and 35.4%, respectively), N-acetyl-5-methoxytryptamine (42.9 and 36.7%, respectively), and P-hydroxybenzoic acid (40.6 and 36.8%, respectively) demonstrated excellent protective and curative activity against rice bacterial leaf blight, which were better than that of zhongshengmycin (38.4 and 34.4%, respectively). In addition, after 2,4-di-tert-butylphenol, N-acetyl-5-methoxytryptamine, and P-hydroxybenzoic acid acted on rice, SOD, POD, and CAD defense enzymes increased under the same condition. In conclusion, these results indicated that the activity and mechanism research of new microbial pesticides were helpful for the prevention and control of rice bacterial diseases.

Design, Synthesis and Antifungal/Nematicidal Activity of Novel 1,2,4-Oxadiazole Derivatives Containing Amide Fragments.

Plant diseases that are caused by fungi and nematodes have become increasingly serious in recent years. However, there are few pesticide chemicals that can be used for the joint control of fungi and nematodes on the market. To solve this problem, a series of novel 1,2,4-oxadiazole derivatives containing amide fragments were designed and synthesized. Additionally, the bioassays revealed that the compound F15 demonstrated excellent antifungal activity against Sclerotinia sclerotiorum (S. sclerotiorum) in vitro, and the EC50 value of that was 2.9 µg/mL, which is comparable with commonly used fungicides thifluzamide and fluopyram. Meanwhile, F15 demonstrated excellent curative and protective activity against S. sclerotiorum-infected cole in vivo. The scanning electron microscopy results showed that the hyphae of S. sclerotiorum treated with F15 became abnormally collapsed and shriveled, thereby inhibiting the growth of the hyphae. Furthermore, F15 exhibited favorable inhibition against the succinate dehydrogenase (SDH) of the S. sclerotiorum (IC50 = 12.5 µg/mL), and the combination mode and binding ability between compound F15 and SDH were confirmed by molecular docking. In addition, compound F11 showed excellent nematicidal activity against Meloidogyne incognita at 200 µg/mL, the corrected mortality rate was 93.2%, which is higher than that of tioxazafen.

Ferulic acid derivatives with piperazine moiety as potential antiviral agents.

BACKGROUND: Plant virus diseases are difficult to control and severely threaten the productivity of crops, which leads to huge financial losses. To discover the new antiviral drugs, 34 novel ferulic acid derivatives with piperazine moiety were synthesized, and the antiviral activities were systematically screened as well. RESULTS: Bioassay results indicated that most of the target compounds had outstanding antiviral activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo. In particular, compound E2 exhibited remarkable curative activities to TMV and CMV with EC50 values of 189.0 and 401.7 µg/mL compared to those for ningnanmycin (387.0, 519.3 µg/mL) and ribavirin (542.1, 721.5 µg/mL). And then the mechanisms of compound E2 were studied by chlorophyll content, differentially expressed proteins and genes tests. CONCLUSION: The excellent antiviral activity of compound E2 was closely associated with the increase in host photosynthesis, which was confirmed by chlorophyll content, differentially expressed proteins and genes assays. Compound E2 can be considered as a lead structure for the discovery of new antiviral agents. © 2022 Society of Chemical Industry.