Synthesis of 4H-Pyrazolo[3,4-d]pyrimidin-4-one Hydrazine Derivatives as a Potential Inhibitor for the Self-Assembly of TMV Particles.

Tobacco mosaic virus coat protein (TMV-CP), as a potential target for the development of antiviral agents, can assist in the long-distance movement of viruses and plays an extremely important role in virus replication and propagation. This work focuses on the synthesis and the action mechanism of novel 4H-pyrazolo[3,4-d] pyrimidin-4-one hydrazine derivatives. The synthesized compounds exhibited promising antiviral activity on TMV. Specifically, compound G2 exhibited high inactivating activity (93%) toward TMV, slightly better than commercial reagent NNM (90%). The action of mechanism was further explored by employed molecular docking, molecular dynamics simulation, microscale thermophoresis, qRT-PCR, and transmission electron microscopy. Results indicated that G2 had the capability to interact with amino acid residues such as Trp352, Tyr139, and Asn73 in the active pocket of TMV-CP, creating strong hydrophobic interactions and thus obstructing the virus's self-assembly.

Trifluoromethylpyridine piperazine derivatives: synthesis and anti-plant virus activity.

BACKGROUND: The cucumber mosaic virus (CMV) is well-known for its expansive host range and distribution, resulting in a detrimental effect on agricultural production, thus making it imperative to implement measures for its control. RESULTS: Novel compounds S1-S28 were synthesized by connecting trifluoromethyl pyridine, amide and piperazine scaffolds. Bioassays indicated that most of the synthesized compounds exhibited good curative effects against CMV, with half maximal effective concentration (EC50 ) values of compounds S1, S2, S7, S8, S10, S11, S15, and S28 being 119.6, 168.9, 197.6, 169.1, 97.9, 73.9, 224.4, and 125.2 µg mL-1 , respectively, which were lower than the EC50 of ningnanmycin (314.7 µg mL-1 ). Compounds S5 and S8 exhibited protective activities with EC50 of 170.8 and 95.0 µg mL-1 , respectively, which were lower than ningnanmycin at 171.4 µg mL-1 . The inactivation activities of S6 and S8 at 500 µg mL-1 were remarkably high at 66.1% and 78.3%, respectively, surpassing that of ningnanmycin (63.5%). Additionally, their EC50 values were more favorable at 22.2 and 18.1 µg mL-1 , respectively, than ningnanmycin (38.4 µg mL-1 ). And molecular docking and molecular dynamics simulation showed compound S8 had better binding with CMV-coat protein, providing a possible explanation for the anti-CMV activity of compound S8. CONCLUSIONS: Compound S8 showed a strong binding affinity to CMV-coat protein and impacted the self-assemble of CMV particles. Compound S8 could be a potential lead compound for discovering a new anti-plant virus candidate. © 2023 Society of Chemical Industry.

The proteomics and metabolomics studies of GZU001 on promoting the Merisis of maize (Zea mays L.) roots.

BACKGROUND: Plant growth regulators are chemicals that regulate plant growth and development, which can regulate hormonal balance and affect plant growth, thereby increasing crop yield and improving crop quality. Our studies have revealed a new compound, GZU001, which could be used as a plant growth regulator. This compound has been observed to affect root elongation in maize significantly. However, the exact mechanism of this phenomenon is still being investigated. RESULTS: Metabolomics and proteomics were used in unison in this study to explore the response pathway and regulation mechanism of GZU001 in promoting maize root elongation. From the appearance, we can see that both roots and plants of maize treated with GZU001 are significantly improved. Maize root metabolism revealed 101 differentially abundant proteins and 79 differentially expressed metabolites. The current study identified altered proteins and metabolites associated with physiological and biochemical processes. GZU001 treatment has been demonstrated to promote primary metabolism, essential for carbohydrates, amino acids, energy, and secondary metabolism. The result suggests that the stimulation of primary metabolism is beneficial for the growth and development of maize and plays a significant role in sustaining metabolism and growth. CONCLUSIONS: This study recorded the changes of related proteins and metabolites in maize roots after GZU001 treatment and provided evidence for this compound's action mode and mechanism in plants.

Design, Synthesis, and Bioactivity of Spiro Derivatives Containing a Pyridine Moiety.

We designed and synthesized a series of pyridine spiro derivatives and evaluated their insecticidal and antiviral activities. Some compounds exhibited good insecticidal and antiviral activities. Notably, the E series of compounds displayed good insecticidal activity against Tetranychus urticae. Compounds E20 (EC50 = 63.68 mg/L) and F4 (EC50 = 47.81 mg/L) exhibited inactivation activities against the tobacco mosaic virus (TMV), which were similar to that of Ningnanmycin (EC50 = 58.01 mg/L). Molecular docking showed that compounds E20 and F4 exhibited satisfactory affinities for the TMV coat protein (TMV-CP), with binding energies (-6.7 and -6.4 kcal/mol, respectively) slightly lower than that of Ningnanmycin (-6.3 kcal/mol). Further, molecular dynamics analysis revealed that compounds E20 and F4 exhibited better binding stability values than Ningnanmycin. Microscale thermophoresis showed that compounds E20 (Kd = 0.053 ± 0.016 µM) and F4 (Kd = 0.045 ± 0.022 µM) bound more strongly to TMV-CP than Ningnanmycin (Kd = 0.10 ± 0.029 µM). The results of transmission electron microscopy showed that these two compounds hindered the self-assembly and growth of TMV. In summary, we showed that these pyridine spiro derivatives could be used as a basis for the research and development of novel pesticides.

Novel trifluoromethylpyridine piperazine derivatives as potential plant activators.

Plant virus diseases seriously affect crop yield, especially tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). The development of plant immune activators has been an important direction in the innovation of new pesticides. Therefore, we designed and synthesized a series of trifluoromethyl pyridine piperazine derivatives (A1-A27), and explored the action mechanism of active compound. The antiviral activity test showed that compounds A1, A2, A3, A9, A10, A16, A17 and A21 possessed higher activities than commercialized ningnanmycin. Particularly, the in vivo antiviral activity indicated that compound A16 showed the most potent protective activity toward TMV (EC50 = 18.4 µg/mL) and CMV (EC50 = 347.8 µg/mL), compared to ningnanmycin (50.2 µg /mL for TMV, 359.6 µg/mL for CMV). The activities of defense enzyme, label -free proteomic and qRT-PCR analysis showed that compound A16 could enhance the defensive enzyme activities of superoxide dismutase (SOD),polyphenol oxidase (PPO) and phenylalanine ammonialyase (PAL), and activate the phenylpropanoid biosynthesis pathway to strenthen the antiviral activities of tobacco. This study provides reliable support for the development of new antiviral pesticides and potential antiviral mechanism.

A briefly overview of the research progress for the abscisic acid analogues.

Abscisic acid (ABA) is an important plant endogenous hormone that participates in the regulation of various physiological processes in plants, including the occurrence and development of somatic embryos, seeddevelopment and dormancy. ABA is called "plant stress resistance factor", while with the limitation of the rapid metabolic inactivation and photoisomerization inactivation of ABA for its large-scale use. Understanding the function and role of ABA in plants is of great significance to promote its application. For decades, scientists have conducted in-depth research on its mechanism of action and signaling pathways, a series of progress were achieved, and hundreds of ABA analogues (similar in structure or function) have been synthesized to develop highly active plant growth regulators and tools to elucidate ABA perception. In this review, we summarize a variety of ABA analogues, especially the ABA receptor analogues, and explore the mechanisms of ABA action and catabolism, which will facilitate the development of novel ABA analogues with high biological activities.

Spiro Derivatives in the Discovery of New Pesticides: A Research Review.

Spiro compounds are biologically active organic compounds with unique structures, found in a wide variety of natural products and drugs. They do not readily lead to drug resistance due to their unique mechanisms of action and have, therefore, attracted considerable attention regarding pesticide development. Analyzing structure-activity relationships (SARs) and summarizing the characteristics of spiro compounds with high activity are crucial steps in the design and development of new pesticides. This review mainly summarizes spiro compounds with insecticidal, bactericidal, fungicidal, herbicidal, antiviral, and plant growth regulating functions to provide insight for the creation of new spiro compound pesticides.

Trifluoromethylpyridine thiourea derivatives: design, synthesis and inhibition of the self-assembly of tobacco mosaic virus particles.

BACKGROUND: Devastating plant virus diseases leading to bad harvests and lower quality of crops have made feeding the beyond seven billion population a huge challenge. Nevertheless, growing resistance and cross resistance of crop protection agents have made this challenge harder. Therefore, an efficient crop protection agent with novel structure and mode of action showing higher efficiency and eco-friendly is urgently needed. RESULTS: The coat protein (CP) of a virus is a potential target for the discovery of new antiviral agents. Antiviral molecules can inhibit infection by obstructing the assembly of virus particles. A series of novel phthalamide-like thiourea derivatives containing trifluoromethylpyridine was designed and synthesized. Most of the compounds exhibited good antiviral activity against tobacco mosaic virus (TMV). Compound 7b showed notable curative, protective and inactivation activities against TMV. Its inactivation half-maximal effective concentration (EC50 ) value (20.5 µg mL-1 ) was better even than commercial ningnanmycin (23.2 µg mL-1 ). Compound 7b also had stronger TMV-CP binding ability than ningnanmycin and destroyed the external shape of TMV particles and hindered the self-assembly of TMV-CP and TMV-RNA. CONCLUSION: These phthalamide-like thiourea derivatives especially compound 7b containing trifluoromethylpyridine are potential lead compounds and inhibitors of TMV particle self-assembly. © 2021 Society of Chemical Industry.

Trifluoromethylpyridine 1,3,4-Oxadiazole Derivatives: Emerging Scaffolds as Bacterial Agents.

A new class of trifluoromethylpyridine 1,3,4-oxadiazole derivatives (6a-6v) was obtained, and their antibacterial activities were evaluated. Some of them exhibited good activity, particularly 6a, which had the highest in vitro activity against Ralstonia solanacearum (R. solanacearum) and Xanthomonas axonopodis pv. citri (Xac). The half-maximal effective concentrations (EC50) were 26.2 and 10.11 µg/mL, respectively, which were lower than those of commercial thiodiazole copper (97.2 and 35.3 µg/mL, respectively). Furthermore, 6q showed much higher activity against Xanthomonas oryzae pv. oryzae (Xoo) with an EC50 value of 7.2 µg/mL; this was superior to bismerthiazol (57.2 µg/mL). Collectively, our findings provide a foundation for the development of trifluoromethylpyridine 1,3,4-oxadiazole derivatives.

Design, Synthesis, and Biological Activity of Novel Ferulic Amide Ac5c Derivatives.

A total of 34 novel ferulic amide Ac5c derivatives were designed and synthesized and their antipest activities were investigated. The results showed that some compounds exhibited excellent in vitro antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo) and X. oryzae pv. oryzicola (Xoc), such as compounds 4q and 5n demonstrated excellent in vitro activity against Xoo, with EC50 values of 4.0, and 1.9 µg/mL, respectively. Compounds 4c, 4h, 4m, 4p, 4q, and 5a had significant in vitro activities against Xoc, with EC50 values of 12.5, 13.9, 9.8 15.0, 9.2, and 19.8 µg/mL, respectively. Moreover, the antibacterial activity in vivo against rice bacterial leaf blight was also evaluated. Scanning electron microscopy (SEM) showed that compound 5n significantly reduced the cell membrane of Xoo, and resulted in cell surface wilting, deformation, breakage, and increased porous attributes. In addition, some of the target compounds also showed moderate biological activity against fungi and acted as potential insecticides.

Design, Synthesis, and Mechanism of Antiviral Acylurea Derivatives Containing a Trifluoromethylpyridine Moiety.

Novel acylurea derivatives 7a-7ab were designed and synthesized by linking the active substructures trifluoromethylpyridine and anthranilic diamide via an acylurea bridge. Most of the title compounds exhibited good activity against tobacco mosaic virus (TMV), particularly compound 7x (EC50 of 211.8 µg/mL), which showed much higher curative activity than ningnanmycin (EC50 of 389.8 µg/mL), and compound 7ab, which showed excellent inactivation activity (EC50 of 36.1 µg/mL), similar to ningnanmycin (EC50 of 23.2 µg/mL). The preliminary mechanism of these derivatives was investigated. Autodocking analysis revealed that compounds 7x and 7ab had good affinity for TMV coat protein (TMV CP), with low binding energies (-7.86 and -8.59 kcal/mol) comparable to ningnanmycin (-8.75 kcal/mol). Molecular dynamics simulation showed that compound 7x had a stable system structure with a better binding free energy (-32.94 kcal/mol) than ningnanmycin (-25.62 kcal/mol). Microscale thermophoresis showed that compound 7x bound more strongly to TMV CP (Kd of 19.8 ± 7.3 µM) than ningnanmycin (Kd of 21.2 ± 7.3 µM). Transmission electron microscopy and self-assembly experiments demonstrated that compounds 7x and 7ab significantly obstructed the self-assembly of TMV RNA and TMV CP. This new acylurea derivative has excellent antiviral activity by targeting TMV CP and inhibiting TMV self-assembly and can be considered a candidate for antiviral applications.

Synthesis of trans- methyl ferulate bearing an oxadiazole ether as potential activators for controlling plant virus.

A series of new ferulic acid derivatives bearing an oxadiazole ether was synthesized by introducing a structure of oxadiazole into trans-ferulic acid via an ether linkage. The synthesized target compounds were evaluated in vivo for their anti-TMV (tobacco mosaic virus) activity, which indicated that some synthesized compounds displayed strong activity for controlling TMV. For protective activity, compounds 6f and 6h had the most activities of 65% and 69.8% at 500 mg L-1, respectively. Compounds 6a, 6b, 6e, 6f and 6h showed > 60% curative activities at 500 mg L-1. Preliminary proteomics analysis showed that compound 6h could regulate the phenylpropanoid biosynthesis pathway and chloroplast function. These results indicated that synthesized novel ferulic acid derivatives could be used for controlling TMV.

Novel Ferulic Amide Ac6c Derivatives: Design, Synthesis, and Their Antipest Activity.

Thirty-eight novel ferulic amide 1-aminocyclohexane carboxylic acid (Ac6c) derivatives D1-D19 and E1-E19 were designed and synthesized, and their antibacterial, antifungal, and insecticidal activities were tested. Most of the synthesized compounds displayed excellent activity againstXanthomonas oryzae pv. oryzae (Xoo), with EC50 values ranging from 11.6 to 83.1 µg/mL better than that of commercial bismerthiazol (BMT, EC50 = 84.3 µg/mL), as well as much better performance compared to that of thiediazole copper (TDC, EC50 = 137.8 µg/mL). D6 (EC50 = 17.3 µg/mL), D19 (EC50 = 29.4 µg/mL), E3 (EC50 = 29.7 µg/mL), E9 (EC50 = 27.0 µg/mL), E10 (EC50 = 18.6 µg/mL), and E18 (EC50 = 20.8 µg/mL) showed much higher activity on Xanthomonas oryzae pv. oryzicola compared with BMT (EC50 = 80.1 µg/mL) and TDC (EC50 = 124.7 µg/mL). In relation to controlling the fungus, Rhizoctonia solani, E1, E10, and E13 had much lower EC50 values of 0.005, 0.140, and 0.159 µg/mL compared to hymexazol at 74.8 µg/mL. Further in vivo experiments demonstrated that E6 and E12 controlled rice bacterial leaf blight disease better than BMT and TDC did. Scanning electron microscopy (SEM) studies revealed that E12 induced the Xoo cell membrane collapse. Moreover, D13 (73.7%), E5 (80.6%), and E10 (73.4%) also showed moderate activity against Plutella xylostella. These results indicated that the synthesized ferulic amide Ac6c derivatives showed promise as candidates for treating crop diseases.

Design, Synthesis, and Bioactivity of α-Ketoamide Derivatives Bearing a Vanillin Skeleton for Crop Diseases.

A series of novel α-ketoamide derivatives bearing a vanillin skeleton were designed and synthesized. Bioactivity tests on virus and bacteria were performed. The results indicated that some compounds exhibited excellent antitobacco mosaic virus (TMV) activities, such as compound 34 exhibited an inactivation activity of 90.1% and curative activity of 51.8% and compound 28 exhibited a curative activity of 54.8% at 500 µg mL-1, which is equivalent to that of the commercial ningnanmycin (inactivation of 91.9% and curative of 51.9%). Moreover, the in vitro antibacterial activity test illustrated that compounds 2, 22, and 33 showed much higher activities than commercial thiodiazole copper, which could be used as lead compounds or potential candidates. The findings of transmission electron microscopy and molecular docking indicated that the synthesized compounds exhibited strong and significant binding affinity to the TMV coat protein and could obstruct the self-assembly and increment of TMV particles. This study revealed that α-ketoamide derivatives bearing a vanillin skeleton could be used as a novel potential pesticide for controlling the plant diseases.

Novel anthranilic amide derivatives bearing the chiral thioether and trifluoromethylpyridine: Synthesis and bioactivity.

Ten anthranilic amides bearing skeletons of chiral thioether and trifluoromethylpyridine (5a-5j) were designed and synthesized. Bioassays indicated that some of compounds had excellent insecticidal activity. For example, compounds 5a, 5e and 5g had the median lethal concentrations (LC50) against Plutella xylostella of 7.3, 8.7 and 8.1 µg/mL respectively. The LC50 of 5a against Ostrinia nubilalis and Pseudaletia separata were 21.7 and 44.2 µg/mL respectively. Anti-TMV tests indicated that some compounds also showed good antiviral activity. For instance, the curative activities of compounds 5b and 5e were 57.2% and 63.6%, and with half maximal effective concentration (EC50) of 304.5 and 203.0 µg/mL, respectively, which were much higher than these of ribavirin (39.4%, EC50 = 819.8 µg/mL) and ningnanmycin (56.2%, EC50 = 361.4 µg/mL). The molecular docking between the most active compounds and ryanodine receptor of the Plutella xylostella were also discussed. Those results indicated that the novel anthranilic amide derivatives in present work were worthy of further research and development as novel pesticides.

Synthesis of Anthranilic Diamide Derivatives Containing Moieties of Trifluoromethylpyridine and Hydrazone as Potential Anti-Viral Agents for Plants.

A series of novel anthranilic diamide derivatives (5a-5ab) containing moieties of trifluoromethylpyridine and hydrazone was designed and synthesized. The synthesized compounds were evaluated in vivo for their activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). Most of the synthesized compounds displayed good to excellent antiviral activities. The compounds 5i, 5k, 5s, 5w, 5x, and 5z had the curative activity over 65% against TMV at the concentration of 500 µg/mL, which were significantly higher than those of ningnanmycin (55.0%) and ribavirin (37.9%). Notably, the curative activity of compound 5i was up to 79.5%, with the EC50 value of 75.9 µg/mL, whereas the EC50 value of ningnanmycin was 362.4 µg/mL. The pot experiments also further demonstrated the significantly curative effect of 5i. Meanwhile, compounds 5h, 5p and 5x displayed more protective activities on TMV than that of ningnanmycin. Moreover, compounds 5a, 5e, 5f, and 5i showed inactivation activity similar to ningnanmycin at 500 µg/mL, and the EC50 value of 5e (41.5 µg/mL) was lower than ningnanmycin (50.0 µg/mL). The findings of transmission electron microscopic (TEM) indicated that the synthesized compounds exhibited strong and significant binding affinity to TMV coat protein (CP) and could obstruct the self-assembly and increment of TMV particles. Microscale thermophoresis (MST) studies on TMV-CP and CMV CP revealed that some of the active compounds, particularly 5i, exhibited a strong binding capability to TMV-CP or CMV-CP. This study revealed that anthranilic diamide derivatives containing moieties of trifluoromethylpyridine and hydrazone could be used as novel antiviral agents for controlling the plant viruses.

Low melting point metal-based flexible 3D biomedical microelectrode array by phase transition method.

In this study, we present a dimension-controllable 3D biomedical microelectrode based on low melting point metals (Bi/In/Sn/Zn alloy) applied using the phase transition method. We have established a process, in which the liquid metal is pumped through a syringe needle of the dispensing system to form a needle shape after cooling at room temperature. PDMS (polydimethylsiloxane) was chosen as the substrate of the electrode as it is amenable to micro-molding and has excellent flexibility. Several key factors, including lifting velocity of the syringe needle and sample temperature were examined as to how they would affect the height, width and depth-width ratio of the electrode, to realize size control of the electrode. Afterwards, the skin-electrode impedance was tested and the results were compared with those of an Ag/AgCl (wet) electrode. The impedance at 10 Hz is 2.357 ±â€¯0.198 MΩ for the 3D microelectrode. From data, the impedance of 3D microelectrode is found to be at the same level as the Ag/AgCl electrode at the frequency of 10 Hz. By increasing the size of the array, the impedance of the low melting point metal electrode and the wet electrode converge. The resistance of the electrode was also measured to describe its stretchability. The electrode can be stretched to a maximum of 42% before it becomes non-conducting. In addition to acquisition of bio-electric signals, our method has strong prospects in the field of bio-sensing.

An adaptive singular spectrum analysis method for extracting brain rhythms of electroencephalography.

Artifacts removal and rhythms extraction from electroencephalography (EEG) signals are important for portable and wearable EEG recording devices. Incorporating a novel grouping rule, we proposed an adaptive singular spectrum analysis (SSA) method for artifacts removal and rhythms extraction. Based on the EEG signal amplitude, the grouping rule determines adaptively the first one or two SSA reconstructed components as artifacts and removes them. The remaining reconstructed components are then grouped based on their peak frequencies in the Fourier transform to extract the desired rhythms. The grouping rule thus enables SSA to be adaptive to EEG signals containing different levels of artifacts and rhythms. The simulated EEG data based on the Markov Process Amplitude (MPA) EEG model and the experimental EEG data in the eyes-open and eyes-closed states were used to verify the adaptive SSA method. Results showed a better performance in artifacts removal and rhythms extraction, compared with the wavelet decomposition (WDec) and another two recently reported SSA methods. Features of the extracted alpha rhythms using adaptive SSA were calculated to distinguish between the eyes-open and eyes-closed states. Results showed a higher accuracy (95.8%) than those of the WDec method (79.2%) and the infinite impulse response (IIR) filtering method (83.3%).