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Background: Plant diseases have been gripping agricultural production, seriously affecting the growth and yields of crops. Marine natural products are an important source for novel drugs discovery. In this work, pityriacitrin marine alkaloids were selected as the parent structures. A series of pityriacitrin alkaloid analogues were rationally designed, synthesized and evaluated for their antiviral activities and fungicidal activities., Result: Most of these compounds were demonstrated to have higher antiviral activities than ribavirin. Particularly, compounds 3a, 3e, 8f, 8g, and 9g displayed higher anti-TMV activities than ningnanmycin at 500 μg·mL -1 . Mechanism research revealed that 3a could bind to TMV CP with an excellent affinity (K a  = 8.67 × 10 6  L·mol -1 ), thus interfere with the assembly of virus particles. These alkaloids also showed broad-spectrum fungicidal activities against eight kinds of phytopathogenic fungi. Compound 5f with 1.43-3.84 μg·mL -1 EC 50 value against three fungi emerged as a new fungicidal candidate., Conclusion: Pityriacitrin alkaloids and their derivatives were synthesized and evaluated for anti-TMV and fungicidal activities for the first time. Compounds 3a and 5f with excellent activities emerged as new candidates for antiviral research and fungicidal research, respectively. Current work provided a new idea for the molecular design and development of novel plant virus and fungi inhibitors in the future. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Background: The invasion of viruses and fungi can cause pathological changes in the normal growth of plants and is an important factor in causing plant infectious diseases. These pathogenic microorganisms can also secrete toxic metabolites, affecting crop quality and posing a threat to human health. In this work, we selected the natural product rutaecarpine as the lead compound to achieve the total synthesis and structural derivation. The antiphytoviral activities of these compounds were systematically studied using tobacco mosaic virus (TMV) as the tested strain, and the structure-activity relationships were summarized., Result: The anti TMV activities of compounds 5a, 5n, 6b, and 7c are significantly higher than that of commercial antiviral agent ningnanmycin. We chose 5n for further antiviral mechanism research, and the results showed that it can directly act on viral particles. The molecular docking results further confirmed the interaction of compound 5n and coat protein (CP). These compounds also exhibited broad-spectrum fungicidal activities against eight plant pathogens. Especially compounds 5j and 5p have significant anti-fungal activities (EC 50 : 5j, 1.76 μg mL -1 ; 5p, 1.59 μg mL -1 ) and can be further studied as leads for plant-based anti-fungal agents., Conclusion: The natural product rutaecarpine and its derivatives were synthesized, and evaluated for their anti-TMV and fungicidal activities. Compounds 5n and 5p with good activities emerged as new antiviral and anti-fungal candidates, respectively. This study provides important information for the research and development of the novel antiviral and fungicidal agents based on rutaecarpine derivatives. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Plant viral diseases, namely 'plant cancer', are extremely difficult to control. Even worse, few antiviral agents can effectively control and totally block viral infection. There is an urgent need to explore and discover novel agrochemicals with high activity and a unique mode of action to manage these refractory diseases. Results: Forty‐one new phenothiazine derivatives were prepared and their inhibitory activity against tobacco mosaic virus (TMV) was assessed. Compound A8 had the highest protective activity against TMV, with a half‐maximal effective concentration (EC50) of 115.67 μg/mL, which was significantly better than that of the positive controls ningnanmycin (271.28 μg/mL) and ribavirin (557.47 μg/mL). Biochemical assays demonstrated that compound A8 could inhibit TMV replication by disrupting TMV self‐assembly, but also enabled the tobacco plant to enhance its defense potency by increasing the activities of various defense enzymes. Conclusion: In this study, novel phenothiazine derivatives were elaborately fabricated and showed remarkable anti‐TMV behavior that possessed the dual‐action mechanisms of inhibiting TMV assembly and invoking the defense responses of tobacco plants. Moreover, new agrochemical alternatives based on phenothiazine were assessed for their antiviral activities and showed extended agricultural application. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: The discovery and identification of targets is of far‐reaching significance for developing novel pesticide candidates and increasing the probability of success. To explore and identify highly effective tobacco mosaic virus (TMV) helicase‐targeted lead structures, a series of novel phosphonate derivatives containing a 1,2,3‐triazole motif were rationally engineered and their antiviral activity was assessed. Results: Bioassay results showed that the optimized B17 exhibited more potent curative activity (EC50 = 271.5 μg mL−1) against TMV in vivo, which was superior to that of commercial Ribavirin (EC50 = 689.3 μg mL−1). B17 presented a stronger binding capacity through binding analysis with helicase, affording a corresponding value of 12.7 μM. Enzyme activity assay showed B17 exhibited excellent inhibitory activity on TMV helicase (39.2% at 300 μM). Furthermore, molecular docking simulations demonstrated that B17 displayed strong hydrogen‐bond interactions (2.1, 2.1, 2.2, and 3.2 Å) with Ala‐33, Gly‐10, Gly‐8, and Glu‐217 of TMV helicase. Encouragingly, transmission electron microscopy analysis revealed that B17 could remarkably disrupt surface morphology and inhibit TMV proliferation. Additionally, these compounds also displayed potential anti‐CMV (cucumber mosaic virus) and antipathogens (Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri) by expanding their applications in agriculture. Conclusion: Current research demonstrated that B17 could be considered as a potential antiviral agent alternative though targeting TMV helicase. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Plant pathogens have led to large yield and quality losses in crops worldwide. The discovery and study of novel agrochemical alternatives based on the chemical modification of bioactive natural products is a highly efficient approach. Here, two series of novel cinnamic acid derivatives incorporating diverse building blocks with alternative linking patterns were designed and synthesized to identify their antiviral capacity and antibacterial activity. RESULTS: The bioassay results demonstrated that most cinnamic acid derivatives had excellent antiviral competence toward tobacco mosaic virus (TMV) in vivo, especially compound A5 (median effective concentration [EC50] = 287.7 μg mL−1), which had a notable protective effect against TMV when compared with the commercial virucide ribavirin (EC50 = 622.0 μg mL−1). In addition, compound A17 had a protective efficiency of 84.3% at 200 μg mL−1 against Xac in plants. Given these outstanding results, the engineered title compounds could be regarded as promising leads for controlling plant virus and bacterial diseases. Preliminary mechanistic studies suggest that compound A5 could enhance the host's defense responses by increasing the activity of defense enzymes and upregulating defense genes, thereby suppressing phytopathogen invasion. CONCLUSION: This research lays a foundation for the practical application of cinnamic acid derivatives containing diverse building blocks with alternative linking patterns in pesticide exploration. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Phytopathogens cause various diseases by parasitizing crops, reducing crop yield and resulting in substantial economic losses in agricultural production. A novel type isolated from the perennial herbaceous Peganum harmala L. seeds, β-carboline alkaloids pegaharine A (PA), has become a hot topic in developing plant-originated green pesticides owing to their significant physiological activities., Results: A scalable bioinspired total synthesis of PA is accomplished in the present work. The systematical biological assay study showed that PA exhibited moderate inhibitory activity against nine tested plant pathogenic fungi and showed significant inhibitory activity in vitro against the three tested plant pathogenic bacteria. Most noteworthy is the inhibitory rates of PA on Xanthomonas oryzae pv. oryzae (Xoo), X. oryzae pv. oryzicola (Xoc) and X. axonopodis pv. citri (Xac) of 93.6%, 92.1% and 86.1%, respectively, which are better than the control drug, bismerthiazol (63.4%, 61.2% and 53.7% at 100 μg mL -1 concentration). Furthermore, the EC 50 value of PA against Xoo, Xoc and Xac was 52.2, 60.0 and 65.1 μg mL -1 , respectively, superior to 72.9, 64.2 and 70.1 μg mL -1 of the control drug. Moreover, the anti-Xoo mechanistic studies revealed that PA exerted its antibacterial effects by increasing the permeability of the bacterial membrane, reducing the extracellular polysaccharide content and inducing morphological changes in bacterial cells., Conclusion: A novel β-carboline alkaloid, PA, was prepared by biomimetic total synthesis. Its significant antibacterial activity was closely related to the permeation of bacterial cell membranes, which was confirmed by anti-Xoo mechanistic studies. More importantly, the structure could be regarded as a model for developing novel bactericides. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Background: With the long‐term use of traditional bactericides and antiviral agents, drug resistance has become increasingly prominent, resulting in impaired crop growth and yields. Based on this, the introduction of small molecular active groups into natural products has become the direction of research for green pesticides. Results: In this study, novel 1,3,4‐oxadiazole sulfonate/carboxylate flavonoid derivatives were explored. Among them, D4 exhibited good inhibitory effects on plant bacteria. It is worth mentioning that D4 (15 μg ml−1) exhibited an excellent median effective concentration (EC50) value against Xanthomonas oryzae pv. oryzae (Xoo), which was better than bismerthiazol (73 μg ml−1) and thiodiazole copper (100 μg ml−1). The EC50 for D4 was much lower than the two positive controls (bismerthiazol, thiodiazole copper), making D4 more potent in this assay of bacterial growth inhibition. In addition, mechanism research using scanning electron microscopy revealed that D4 could cause deformation or rupture of the cell membranes of Xoo and Pseudomonas syringae pv. actinidiae. Moreover, D4 exhibited the best EC50 for in vivo curative (132 μg ml−1) and protective (101 μg ml−1) activities against tobacco mosaic virus, which were more effective than ningnanmycin. Microscale thermophoresis data suggested that D4 [dissociation constant (Kd) = 0.038 ± 0.011 μmol L−1] exhibited a stronger binding capacity than the control agent ningnanmycin (Kd = 4.707 ± 2.176 μmol L−1). Conclusion: The biological activity data and mode of action demonstrated that D4 had the best antibacterial and antiviral effects. Compound D4 discovered in the current work may be a very promising agricultural drug. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

BACKGROUND Plant diseases caused by viruses and fungi have caused great losses to crop quality and yield. The discovery of novel and efficient antiviral and antiphytopathogenic‐fungus agents is urgently needed. It is the most important pesticide innovation strategy to find active compounds from natural products. Here, glyantrypine‐family alkaloids were taken as the parent structures and a series of their derivatives were designed through molecular splicing, ring expansion, and ring contraction strategies, and synthesized. The anti‐tobacco mosaic virus (TMV) activities and antifungal activities of these alkaloids were systematically investigated for the first time. RESULT: The antiviral activities of compounds 7bb, 7bc, 11c, 18b, 18d, 28d, and 28e are equivalent to or better than that of ribavirin (inhibitory rates 39%, 37%, and 40% at 500 μg mL−1 for inactivation, curative, and protection activity in vivo, respectively). Compounds 18d and 28d with good antiviral activities were selected for antiviral mode of action studies, which indicated that these alkaloids could achieve good antiviral effects by inhibiting TMV particle extension during assembly. These compounds also exhibited broad‐spectrum fungicidal activities. CONCLUSION: Glyantrypine‐family alkaloids and their derivatives were synthesized and evaluated for anti‐TMV and fungicidal activities for the first time. Compounds 18d and 28d with excellent antiviral activities and compound 7bc with remarkable fungicidal activity emerged as novel lead compounds. This study lays a foundation for the application of glyantrypine alkaloids in plant protection. [ABSTRACT FROM AUTHOR]

BACKGROUND: Food is an important strategic material related to national economy and people's livelihood. Plant diseases seriously affect crop yield and quality. Marine natural products are an important source for novel drugs discovery. In this work, meridianin alkaloids were selected as the parent structure. A series of meridianin alkaloid analogues were rationally designed, synthesized and evaluated for their antiviral activities and fungicidal activities. RESULT: These compounds were found to have good antiviral and fungicidal activities for the first time. The structure–activity relationship (SAR) research revealed that introducing bromine atom at the 5‐position of indole ring is beneficial to antiviral activity, but introducing methoxy group is not conducive. Introducing bromine atom at the 6‐position of indole ring or nitrogen atom at the 7‐position of the indole ring resulted in lower antiviral activity. Most of the meridianin derivatives showed higher anti‐TMV activities at 500 μg mL−1 than Ribavirin, especially for compounds 6c, 8a and 10a. All of the compounds also displayed broad spectrum fungicidal activities against 14 kinds of phytopathogenic fungi at 50 μg mL−1. CONCLUSION: Compound 6c with relatively simple structure and excellent antiviral activity, which is similar to that of Ningnanmycin, emerged as novel anti‐TMV lead compound. Compound 5d with broad spectrum and high effect fungicidal activity emerged as a new fungicidal lead compound. Current research lays a solid foundation for the application of meridianin alkaloids in crop protection. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]