anti-TMV Activity Research Articles

Design, Synthesis, Anti-TMV Activity, and Structure-Activity Relationships of Seco-pregnane C21 Steroids and Their Derivatives.

seco-pregnane C21 steroids exhibit high antiviral activity against the tobacco mosaic virus (TMV). However, the structural modification of seco-pregnane C21 steroids and the structure-activity relationship (SAR) of the modified compounds remain unevaluated. Hence, the present study investigated how variations in the original skeletons of natural seco-pregnane C21 steroids affect their antiviral activity. A series of glaucogenin C and A derivatives were designed and synthesized for the first time, and their anti-TMV activity was evaluated. Bioassay results showed that most of the newly designed derivatives exhibited good to excellent antiviral activity; among these derivatives, 5g, 5j, and 5l with higher antiviral activity than that of ningnanmycin emerged as new antiviral candidates. Reverse transcription-polymerase chain reaction and Western blotting assay revealed reduced levels of TMV coat protein (TMV-CP) gene transcription and TMV-CP protein expression, which confirmed the antiviral activity of these derivatives. These compounds also downregulated the expression of NtHsp70-1 and NtHsp70-061. Computational simulations indicated that 5l displayed strong van der Waals energy and electrostatic with the TMV coat protein, affording a lower binding energy (ΔGbind = -56.2 kcal/mol) compared with Ribavirin (ΔGbind = -47.6 kcal/mol). The SAR of these compounds was also evaluated, which demonstrated for the first time that substitutions at C-3 and double bonds of C-5/C-6 and C-13/C-18 are crucial for maintaining high anti-TMV activity.

Synthesis, Anti-TMV Activities, and Action Mechanisms of a Novel Cytidine Peptide Compound.

Cytidine has a broad range of applications in the pharmaceutical field as an intermediate of antitumor or antiviral agent. Here, a series of new cytidine peptide compounds were synthesized using cytidine and Boc group-protected amino acids and analyzed for their antiviral activities against tobacco mosaic virus (TMV). Among these compounds, the structure of an effective antiviral cytidine peptide SN11 was characterized by 1H NMR, 13C NMR, and high-resolution mass spectrometer. The compound SN11 has a molecular formula of C15H22N6O8 and is named 2-amino-N-(2- ((1- (3,4-dihydroxy-5-(hydroxymethyl) tetrahydrofuran-2-yl) -2-oxo-1,2-dihydropyrimidin-4-yl) amino) -2-oxyethyl) amino). The protection, inactivation, and curation activities of SN11 at a concentration of 500 μg/mL against TMV in Nicotiana glutinosa were 82.6%, 84.2%, and 72.8%, respectively. SN11 also effectively suppressed the systemic transportation of a recombinant TMV carrying GFP reporter gene (p35S-30B:GFP) in Nicotiana benthamiana by reducing viral accumulation to 71.3% in the upper uninoculated leaves and inhibited the systemic infection of TMV in Nicotiana tabacum plants. Furthermore, the results of RNA-seq showed that compound SN11 induced differential expression of genes involved in the biogenesis and function of ribosome, plant hormone signal transduction, plant pathogen interaction, and chromatin. These results validate the antiviral mechanisms of the cytidine peptide compound and provide a theoretical basis for their potential application in the management of plant virus diseases.

Design, synthesis, and biological activities of arecoline derivatives containing 1,3,4-oxadiazole structure

Pesticides play an important role in the development of agriculture, as they can prevent and control crop diseases and pests, improve crop yield and quality. However, the abuse and improper use of pesticides can lead to negative impacts such as environmental pollution and pest resistance issues. There is an urgent need to develop green, safe, and efficient pesticides. In this work, natural product arecoline was selected as parent structure, a series of arecoline derivatives were designed, synthesized, and systematically investigated antiviral activities against tobacco mosaic virus (TMV). These compounds were found to have good to excellent anti-TMV activities for the first time. The antiviral activities of 4a, 4 h, 4 l, 4p, 6a, 6c, and 6f are higher than that of ningnanmycin. Compounds 4 h (EC50 value 146 µg/mL) and 4p (EC50 value 161 µg/mL) with simple structures and excellent activities emerged as new antiviral candidates. We chose 4 h to further investigate the antiviral mechanism, which revealed that it can cause virus fragmentation by acting on the viral coat protein (CP). We further validated this result through molecular docking. These compounds also displayed broad-spectrum fungicidal activities against 8 plant pathogenic fungi. This work lays the theoretical foundation for the application of arecoline derivatives in the agricultural field.

Structural Simplification of Podophyllotoxin: Discovery of γ-Butyrolactone Derivatives as Novel Antiviral Agents for Plant Protection.

Natural products are a valuable resource for the discovery of novel crop protection agents. A series of γ-butyrolactone derivatives, derived from the simplification of podophyllotoxin's structure, were synthesized and assessed for their efficacy against tobacco mosaic virus (TMV). Several derivatives exhibited notable antiviral properties, with compound 3g demonstrating the most potent in vivo anti-TMV activity. At 500 μg/mL, compound 3g achieved an inactivation effect of 87.8%, a protective effect of 71.7%, and a curative effect of 67.7%, surpassing the effectiveness of the commercial plant virucides ningnanmycin and ribavirin. Notably, the syn-diastereomer (syn-3g) exhibited superior antiviral activity compared to the anti-diastereomer (anti-3g). Mechanistic studies revealed that syn-3g could bind to the TMV coat protein and interfere with the self-assembly process of TMV particles. These findings indicate that compound 3g, with its simple chemical structure, could be a potential candidate for the development of novel antiviral agents for crop protection.

Design, synthesis and antiviral activity of indole derivatives containing quinoline moiety.

A series of indole derivatives containing quinoline structures were designed and synthesized. The synthesized compounds were characterized by NMR and HRMS. And W14 was performed by single crystal X-ray diffraction experiments. The antiviral activity studies showed that some of the target compounds possessed significant activity against tobacco mosaic virus (TMV). In particular, W20 had significant activity. The results of in vivo anti-TMV activity assay showed that W20 possessed the best curative and protective activities with EC50 values of 84.4 and 65.7 μg/mL, which were better than ningnanmycin (NNM) 205.1 and 162.0 μg/mL, respectively. The results of Microscale thermophoresis (MST) showed that W20 had a strong binding affinity for the tobacco mosaic virus coat protein (TMV-CP) with a dissociation constant (Kd) of 0.00519 μmol/L, which was superior to that of NNM (1. 65320 μmol/L). The molecular docking studies were in accordance with the experimental results. In addition, the determination of malondialdehyde (MDA) content in tobacco leaves showed that W20 improved the disease resistance of tobacco. Overall, this study shows that indole derivatives containing quinoline can be used as new antiviral agents for plant viruses for further research.

The Use of Bacteria, Actinomycetes and Fungi in the Bioprotection of Solanaceous Crops against Tobacco Mosaic Virus (TMV)

Tobacco mosaic virus (TMV) is one of the most persistent and infectious plant viruses. The substantial economic losses caused by TMV in the production of tobacco and vegetables (especially in the Solanaceae family) are prompting the introduction of innovative solutions that effectively inhibit infection by this pathogen. Biological control agents based on bacteria of the genera Pseudomonas, Bacillus, Pantoea and actinomycetes are becoming increasingly popular in the fight against TMV. Some fungi, including Fusarium spp., Trichoderma spp., Alternaria spp. and Sepedonium spp., as well as wood-rotting fungi, also exhibit high anti-TMV activity. This article presents a comprehensive review of recent scientific advances in the bioprotection of selected solanaceous crops against TMV. It provides information on the structure of the virus, its host range, pathogenicity and the severity of losses caused in pepper, tomato and tobacco production. The review characterises environmentally safe techniques involving biological control agents naturally occurring in the environment and the bioactive compounds extracted from them. It also identifies their effects on crops at the morphological, physiological and molecular levels. In addition, the manuscript outlines prospects for the future applications of beneficial micro-organisms and active compounds derived from them in the protection against TMV.

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.

Extraction optimization, physicochemical properties, and inhibitory effect against tobacco mosaic virus of the protein from discarded tobacco leaves

Plant proteins have been attracting increasing attention due to their significant antiviral activity against tobacco mosaic virus (TMV). This paper aimed to investigate the tobacco endogenous protein and the anti-TMV effects. Firstly, the extraction of protein from discarded tobacco leaves (DTLP) was optimized by response surface methodology (RSM). The maximum DTLP yield reached to 8.32 % under the condition of solid-liquid ratio 1:19, temperature 60 °C and pH 12. DTLP was rich in hydrophilic amino acids, such as aspartic acid (8.08 ± 0.34 g/100 g) and glutamic acid (8.02 ± 0.42 g/100 g). DTLP structure was compact and stable with a denaturation temperature of 99.7 °C. Furthermore, the anti-TMV experiments revealed that DTLP showed inactive and protective activities against TMV with inhibitory rates (79.2 % and 75.4 %, respectively) at 500 µg/mL, and inhibited the polymerization of TMV-CP to damage TMV particles. In addition, DTLP increased the expressions of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) and phenylalanine ammonia lyase (PAL) in tobacco leaves by 1.55, 1.18, 9.13 and 2.92 times, respectively. Transcriptomics further verified that DTLP increased the expressions of TGA, WRKY, and PR1 genes for up-regulating the salicylic acid (SA) and pathogenesis-related proteins (PRs), thereby improving the system resistance of tobacco plants. Therefore, DTLP could be potentially developed as an alternative drug to treat plant viral diseases due to its broad-spectrum anti-TMV activity.

Repairing Host Damage Caused by Tobacco Mosaic Virus Stress: Design, Synthesis, and Mechanism Study of Novel Oxadiazole and Arylhydrazone Derivatives.

Tobacco mosaic virus (TMV), as one of the most traditional and extensive biological stresses, poses a serious threat to plant growth and development. In this work, a series of 1-phenyl/tertbutyl-5-amino-4-pyrazole oxadiazole and arylhydrazone derivatives was synthesized. Bioassay evaluation demonstrated that the title compounds (P1-P18) without a "thioether bond" lost their anti-TMV activity, while some of the ring-opening arylhydrazone compounds exhibited superior in vivo activity against TMV in tobacco. The EC50 value of title compound T8 for curative activity was 139 μg/mL, similar to that of ningnanmycin (NNM) (EC50 = 152 μg/mL). Safety analysis revealed that compound T8 had no adverse effects on plant growth or seed germination at a concentration of 250 μg/mL. Morphological observation revealed that compound T8 could restore the leaf tissue of a TMV-stressed host and the leaf stomatal aperture to normal. A mechanism study further revealed that compound T8 not only restored the photosynthetic and growth ability of the damaged host to normal levels but also enhanced catalase (CAT) activity and reduced the content of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in the damaged host, thereby reducing the oxidation damage to the host. TMV-green fluorescent protein (GFP) experiments further demonstrated that compound T8 not only slowed the transmission speed of TMV in the host but also inhibited its reproduction. All of the experimental results demonstrated that compound T8 could reduce the oxidative damage caused by TMV stress and regulate the photosynthetic ability of the host, achieving the ability to repair damage, to make the plant grow normally.

Antiviral activity evaluation and action mechanism of chalcone derivatives containing phenoxypyridine.

In this paper, a series of phenoxypyridine-containing chalcone derivatives (L1-L28) were designed and synthesized, characterized on NMR and HRMS. Ningnanmycin (NNM) was used as a control agent. The results of the antiviral activity testing showed that the curative activity EC50 values of L1 and L4 against TMV were 140.5 and 90.7μg/mL, respectively, which were superior to that of NNM (148.3μg/mL). The EC50 values of 154.1, 102.6 and 140.0μg/mL for the anti-TMV protective activities of L1, L4 and L15 were superior to that of NNM (188.2μg/mL). The mechanism of action between L4 and NNM and tobacco mosaic virus capsid protein (TMV-CP) was preliminarily investigated. The results of microscale thermophoresis (MST) experiments showed that L4 had a strong binding affinity for TMV-CP with a dissociation constant Kd value of 0.00149µM, which was better than that of NNM (2.73016µM). The results of molecular docking experiments showed that L4 formed shorter hydrogen bonds with amino acid residues of TMV-CP than NNM and formed more amino acid residues than NNM, which indicated that L4 was more tightly bound to TMV-CP. This study suggested that phenoxypyridine-containing chalcone derivatives can be used as new anti-TMV drugs through further research and development.

Novel Cyclopenta[c]pyridine Derivatives Based on Natural Cerbinal as Potential Agrochemical Anti-TMV Agents and Insecticides.

Based on natural cerbinal, a series of novel 4-bit modified cyclopenta[c]pyridine derivatives containing a substituted amide or ester moiety were designed and synthesized for the first time. Their structures were systematically characterized by NMR and high-resolution mass spectra (HRMS). The anti-TMV activities, such as protection, inactivation, and curative effects in vivo, were evaluated methodically. The lethal activities of the target compounds against the agriculturally common pests Plutella xylostella larvae and Aphis laburni kaltenbach were evaluated by the immersion method. The bioassay results indicated that most of the target compounds exhibited good to excellent anti-TMV activity levels, good lethal activity against P. xylostella larvae at 600 μg/mL, and greater insecticidal activities against A. laburni Kaltenbach compared to the plant-derived insecticide rotenone. The binding mode of cerbinal and cyclopenta[c]pyridine derivatives 4b, 4p, and 4v with the TMV protein was studied with a molecular docking method, which indicated that the functional group of the 2- and 4-positions is vital for anti-TMV activity. The systematic research provides strong evidence that these novel 4-bit modified cyclopenta[c]pyridine derivatives could become potential agrochemical insecticides and anti-TMV agents.

Separation of anti-TMV active components and modes of action of Omphalia lapidescens

BackgroundOmphalia lapidescens is a saprophytic and parasitic fungus belonging to the Polypora genus of Tricholomataceae. It has repellent, insecticidal, anti-inflammatory and immunomodulatory effects. ResultThis study found that the extract of O. lapidescens had significant anti-TMV activity, and the main active component was homopolysaccharide LW-1 by Bioassay-guided fractionation. LW-1 is a glucan with β-(1,3) glucoside bond as the main chain and β-(1,6) glucoside bond as the branch chain, with molecular weight in the range of 172,916–338,827 Da. The protective and inactive efficacies of LW-1(100 mg/L) against TMV were 78.10% and 48.20%, but had no direct effect on the morphology of TMV particles. The results of mechanism of action showed that LW-1 induced the increase of the activity of defense enzymes such as POD, SOD and PAL in Nicotiana glutinosa. The overexpression of resistance genes such as NPR1, PR1 and PR5, and the increase of SA content. Further transcriptome sequencing showed that LW-1 activated MAPK signaling pathway, plant-pathogen interaction pathway and glucosinolide metabolic pathway in Arabidopsis thaliana. Besides, LW-1 induced crops resistance against plant pathogenic fungi. ConclusionTaken together, the anti-TMV mechanism of LW-1 was to activate MAPK signaling pathway, inducing overexpression of resistance genes, activating plant immune system, and improving the synthesis and accumulation of plant defencins such as glucosinolide. LW-1-induced plant disease resistance has the advantages of broad spectrum and long duration, which has the potential to be developed as a new antiviral agent or plant immune resistance inducer.

Three new flavones from the whole plants of Cassia auriculata Linn. and their antiviral activities

Cassia auriculata, a widely grown medicinal plant in China, has not been fully studied in terms of its secondary metabolites. In our pursuit of new bioactive metabolites from Cassia plants, we conducted a phytochemical reinvestigation on C. auriculata. This investigation resulted in the isolation of three new (1−3) and six known (4−9) flavones. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D NMR techniques. Interestingly, Compounds 1-3 are rare flavones bearing an unusual (4-methylfuran-2-yl)methyl moiety. In addition, Compounds 1-3 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that Compounds 1–3 exhibited potential anti-TMV activities with inhibition rates of 26.8%, 30.5% and 34.6% at a concentration of 20 μM, respectively, and these rates are close to that of the positive control. Compounds 1-9 were also tested for their anti-rotavirus activities. The results revealed that 1–9 exhibited potential anti-rotavirus activity with therapeutic index (TI) values in the range of 13.3–20.8. These values are lower than that of the positive control (with a therapeutic index of 23.4).

Carboline Alkaloids from the Cigar Tobacco-Derived Fungi Aspergillus sp. and Their Anti-TMV Activity

Carboline Alkaloids from the Cigar Tobacco-Derived Fungi Aspergillus sp. and Their Anti-TMV Activity

Two New Phenolic Glycosides from Thalictrum scabrifolium and Their Anti-TMV Activities

Two New Phenolic Glycosides from Thalictrum scabrifolium and Their Anti-TMV Activities

Limonene anti-TMV activity and its mode of action

The main component of orange peel essential oil is limonene. Limonene is a natural active monoterpene with multiple functions, such as antibacterial, antiseptic and antitumor activity, and has important development value in agriculture. This study found that limonene exhibited excellent anti-tobacco mosaic virus (TMV) bioactivity, with results showing that its protection activity, inactivation activity, and curative activity at 800 μg/mL were 84.93%, 59.28%, and 58.89%, respectively—significantly higher than those of chito-oligosaccharides. A direct effect of limonene on TMV particles was not observed, but limonene triggered the hypersensitive response (HR) in tobacco. Further determination of the induction activity of limonene against TMV demonstrated that it displayed good induction activity at 800 μg/mL, with a value of 60.59%. The results of physiological and biochemical experiments showed that at different treatment days, 800 μg/mL limonene induced the enhancement of defense enzymes activity in tobacco, including of SOD, CAT, POD, and PAL, which respectively increased by 3.2, 4.67, 4.12, and 2.33 times compared with the control (POD and SOD activities reached highest on the seventh day, and PAL and CAT activities reached highest on the fifth day). Limonene also enhanced the relative expression levels of pathogenesis related (PR) genes, including NPR1, PR1, and PR5, which were upregulated 3.84-fold, 1.86-fold and 1.71-fold, respectively. Limonene induced the accumulation of salicylic acid (SA), and increased the relative expression levels of genes related to SA biosynthesis (PAL) and reactive oxygen species (ROS) burst (RBOHB), which respectively increased by 2.76 times and 4.23 times higher than the control. Systemic acquired resistance (SAR) is an important plant immune defense against pathogen infection. The observed accumulation of SA, the enhancement of defense enzymes activity and the high-level expression of defense-related genes suggested that limonene may induce resistance to TMV in tobacco by activating SAR mediated by the SA signaling pathway. Furthermore, the experimental results demonstrated that the expression level of the chlorophyll biosynthesis gene POR1 was increased 1.72-fold compared to the control in tobacco treated with 800 μg/mL limonene, indicating that limonene treatment may increase chlorophyll content in tobacco. The results of pot experiment showed that 800 μg/mL limonene induced plant resistance against Sclerotinia sclerotiorum (33.33%), Phytophthora capsici (54.55%), Botrytis cinerea (50.00%). The bioassay results indicated that limonene provided broad-spectrum and long-lasting resistance to pathogen infection. Therefore, limonene has good development and utilization value, and is expected to be developed into a new botanical-derived anti-virus agent and plant immunity activator in addition to insecticides and fungicides.

C-Alkylated flavonoids from the whole plants of Desmodium caudatum and their anti-TMV activity.

Natural products are important sources of biopesticides to control plant virus, and flavonoids are identified as promising anti-tobacco mosaic virus (TMV) agents. Since Desmodium caudatum is a rich source of flavonoids, this study focuses on the discovery of the new anti-TMV active flavonoids from D. caudatum and their possible mode of action. Three new (compounds 1-3) and nine known (compounds 4-12) C-alkylated flavonoids were isolated from D. caudatum. To the best of our knowledge, the framework of 1-3 was reported in natural products for the first time. In addition, 1-3, 5, and 6 showed notable anti-TMV activity with inhibition rates in the range of 35.8-64.3% at a concentration of 50 μg/mL, and these rates are higher than that of positive control (with inhibition rates of 34.6% ± 2.8). In addition, the structure-activity relationship study revealed that the (pyrrol-2-yl)methyl moiety on flavone can significantly increases the activity. This result is helpful to find new anti-TMV inhibitors. C-Alkylated flavonoids showed potent activities against TMV with multiple modes of actions. The increase of defense-related enzyme activities, up-regulate the expression of defense related genes, down-regulate the expression of Hsp70 protein by inhibiting the related Hsp genes that are involved in tobacco resistance to TMV. By the actions mentioned earlier, the infection of TMV was influenced, thereby achieving the effects of control of TMV. The successful isolation of the earlier-mentioned flavonoids provide the new source of biopesticides to TMV proliferation, and also contribute to the utilization of D. caudatum. © 2023 Society of Chemical Industry.

Design, Synthesis and Various Bioactivity of Acylhydrazone-Containing Matrine Analogues.

Compounds with acylhydrazone fragments contain amide and imine groups that can act as electron donors and acceptors, so they are easier to bind to biological targets and thus generally exhibit significant biological activity. In this work, acylhydrazone fragments were introduced to the C-14 or C-11 position of matrine, a natural alkaloid, aiming to enhance their biological activities. The result of this bioassay showed that many synthesized compounds exhibited excellent anti-virus activity against the tobacco mosaic virus (TMV). Seventeen out of 25 14-acylhydrazone matrine derivatives and 17 out of 20 11-butanehydrazone matrine derivatives had a higher inhibitory activity against TMV than the commercial antiviral agent Ribavirin (the in vitro activity, in vivo inactivation, curative and protection activities at 500 µg/mL were 40.9, 36.5 ± 0.9, 38.0 ± 1.6 and 35.1 ± 2.2%, respectively), and four 11-butanehydrazone matrine derivatives even had similar to or higher activity than the most efficient antiviral agent Ningnanmycin (55.4, 57.8 ± 1.4, 55.3 ± 0.5 and 60.3 ± 1.2% at 500 µg/mL for the above four test modes). Among them, the N-benzyl-11-butanehydrazone of matrine formed with 4-bromoindole-3-carboxaldehyde exhibited the best anti-TMV activity (65.8, 71.8 ± 2.8, 66.8 ± 1.3 and 69.5 ± 3.1% at 500 µg/mL; 29, 33.5 ± 0.7, 24.1 ± 0.2 and 30.3 ± 0.6% at 100 µg/mL for the above four test modes), deserving further investigation as an antiviral agent. Other than these, the two series of acylhydrazone-containing matrine derivatives were evaluated for their insecticidal and fungicidal activities. Several compounds were found to have good insecticidal activities against diamondback moth (Plutella xylostella) and mosquito larvae (Culex pipiens pallens), showing broad biological activities.

Discovery of Resveratrol and its Derivatives as Novel Antiviral and Anti- Phytopathogenic-Fungus Agents.

Plant diseases caused by viruses and pathogens have posed a serious threat to global agricultural production and are difficult to control. Natural products have always been a valuable source for lead discovery in medicinal and agricultural chemistry. The natural product resveratrol was found to have good antiviral activity against the tobacco mosaic virus (TMV) and fungicidal activities against 14 kinds of phytopathogenic fungi. The aim of this work was to design, synthesize a series of derivatives of resveratrol, and evaluate their antiviral and fungicidal activities systematically. Novel resveratrol sulfonate derivatives were prepared by a convenient synthesis method from resveratrol, alkyl sulfonyl chloride, aryl sulfonyl chloride, and heterocyclic sulfonyl chloride. Their structures were also identified by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS). Most of the targets were obtained at a high yield. Compounds I-2, I-5, I-10, II-2, and II-4, with excellent antiviral activities, showed higher anti-TMV activities than those of lead compounds and commercial ribavirin (inhibitory rates of 38, 37, and 38% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively). In particular, compounds I-5, I-10, II-2, and II-4 displayed similar inhibitory effects as ningnanmycin (inhibitory rates of 54, 56, and 58% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively), the best antiviral agent at present, thereby emerging as new antiviral pilot compounds. Further fungicidal activity tests showed that resveratrol derivatives also displayed broad-spectrum fungicidal activities. The anti-TMV activities of these compounds were discovered for the first time. Some of these simply structured compounds showed higher TMV inhibitory effects than ribavirin. The current study provided valuable insights into the antiviral and fungicidal activities of resveratrol derivatives, but more modification of the structure should be conducted.

Natural Products for Pesticides Discovery: Structural Diversity Derivation and Biological Activities of Naphthoquinones Plumbagin and Juglone.

Plant diseases and insect pests seriously affect the yield and quality of crops and are difficult to control. Natural products are an important source for the discovery of new pesticides. In this work, naphthoquinones plumbagin and juglone were selected as parent structures, and a series of their derivatives were designed, synthesized and evaluated for their fungicidal activities, antiviral activities and insecticidal activities. We found that the naphthoquinones have broad-spectrum anti-fungal activities against 14 types of fungus for the first time. Some of the naphthoquinones showed higher fungicidal activities than pyrimethanil. Compounds I, I-1e and II-1a emerged as new anti-fungal lead compounds with excellent fungicidal activities (EC50 values: 11.35-17.70 µg/mL) against Cercospora, arachidicola Hori. Some compounds also displayed good to excellent antiviral activities against the tobacco mosaic virus (TMV). Compounds I-1f and II-1f showed similar level of anti-TMV activities with ribavirin, and could be used as new antiviral candidates. These compound also exhibited good to excellent insecticidal activities. Compounds II-1d and III-1c displayed a similar level of insecticidal activities with matrine, hexaflumuron and rotenone against Plutella xylostella. In current study, plumbagin and juglone were discovered as parent structures, which lays a foundation for their application in plant protection.