Identification of novel 4-substituted 7H-pyrrolo[2,3-d]pyrimidine derivatives as new FtsZ inhibitors: Bioactivity evaluation and computational simulation.

Bacterial infections and the consequent outburst of bactericide-resistance issues are fatal menace to both global health and agricultural produce. Hence, it is crucial to explore candidate bactericides with new mechanisms of action. The filamenting temperature-sensitive mutant Z (FtsZ) protein has been recognized as a new promising and effective target for new bactericide discovery. Hence, using a scaffold-hopping strategy, we designed new 7H-pyrrolo[2,3-d]pyrimidine derivatives, evaluated their antibacterial activities, and investigated their structure-activity relationships. Among them, compound B6 exhibited the optimal in vitro bioactivity (EC50 = 4.65 µg/mL) against Xanthomonas oryzae pv. oryzae (Xoo), which was superior to the references (bismerthiazol [BT], EC50 = 48.67 µg/mL; thiodiazole copper [TC], EC50 = 98.57 µg/mL]. Furthermore, the potency of compound B6 in targeting FtsZ was validated by GTPase activity assay, FtsZ self-assembly observation, fluorescence titration, Fourier-transform infrared spectroscopy (FT-IR) assay, molecular dynamics simulations, and morphological observation. The GTPase activity assay showed that the final IC50 value of compound B6 against XooFtsZ was 235.0 µM. Interestingly, the GTPase activity results indicated that the B6-XooFtsZ complex has an excellent binding constant (KA = 103.24 M-1). Overall, the antibacterial behavior suggests that B6 can interact with XooFtsZ and inhibit its GTPase activity, leading to bacterial cell elongation and even death. In addition, compound B6 showed acceptable anti-Xoo activity in vivo and low toxicity, and also demonstrated a favorable pharmacokinetic profile predicted by ADMET analysis. Our findings provide new chemotypes for the development of FtsZ inhibitors as well as insights into their underlying mechanisms of action.

Progressive Optimization of Lanthanide Nanoparticle Scintillators for Enhanced Triple-Activated Radioluminescence Imaging.

Lanthanide nanoparticle (LnNP) scintillators exhibit huge potential in achieving radionuclide-activated luminescence (radioluminescence, RL). However, their structure-activity relationship remains largely unexplored. Herein, progressive optimization of LnNP scintillators is presented to unveil their structure-dependent RL property and enhance their RL output efficiency. Benefiting from the favorable host matrix and the luminescence-protective effect of core-shell engineering, NaGdF4 : 15 %Eu@NaLuF4 nanoparticle scintillators with tailored structures emerged as the top candidates. Living imaging experiments based on optimal LnNP scintillators validated the feasibility of laser-free continuous RL activated by clinical radiopharmaceuticals for tumor multiplex visualization. This research provides unprecedented insights into the rational design of LnNP scintillators, which would enable efficient energy conversion from Cerenkov luminescence, γ-radiation, and ß-electrons into visible photon signals, thus establishing a robust nanotechnology-aided approach for tumor-directed radio-phototheranostics.

Development of [177Lu]Lu-LNC1003 for radioligand therapy of prostate cancer with a moderate level of PSMA expression.

PURPOSE: Evans blue as an albumin binder has been widely used to improve pharmacokinetics and enhance tumor uptake of radioligands, including prostate-specific membrane antigen (PSMA) targeting agents. The goal of this study is to develop an optimal Evans blue-modified radiotherapeutic agent that could maximize the absolute tumor uptake and tumor absorbed dose thus the therapeutic efficacy to allow treatment of tumors even with moderate level of PSMA expression. METHODS: [177Lu]Lu-LNC1003 was synthesized based on PSMA-targeting agent and Evans blue. Binding affinity and PSMA targeting specificity were verified through cell uptake and competition binding assay in 22Rv1 tumor model that has moderate level of PSMA expression. SPECT/CT imaging and biodistribution studies in 22Rv1 tumor-bearing mice were performed to evaluate the preclinical pharmacokinetics. Radioligand therapy studies were conducted to systematically assess the therapeutic effect of [177Lu]Lu-LNC1003. RESULTS: LNC1003 showed high binding affinity (IC50 = 10.77 nM) to PSMA in vitro, which was comparable with that of PSMA-617 (IC50 = 27.49 nM) and EB-PSMA-617 (IC50 = 7.91 nM). SPECT imaging of [177Lu]Lu-LNC1003 demonstrated significantly improved tumor uptake and retention as compared with [177Lu]Lu-EB-PSMA and [177Lu]Lu-PSMA-617, making it suitable for prostate cancer therapy. Biodistribution studies further confirmed the remarkably higher tumor uptake of [177Lu]Lu-LNC1003 (138.87 ± 26.53%ID/g) over [177Lu]Lu-EB-PSMA-617 (29.89 ± 8.86%ID/g) and [177Lu]Lu-PSMA-617 (4.28 ± 0.25%ID/g) at 24 h post-injection. Targeted radioligand therapy results showed noteworthy inhibition of 22Rv1 tumor growth after administration of a single dose of 18.5 MBq [177Lu]Lu-LNC1003. There was no obvious antitumor effect after [177Lu]Lu-PSMA-617 treatment under the same condition. CONCLUSION: In this study, [177Lu]Lu-LNC1003 was successfully synthesized with high radiochemical purity and stability. High binding affinity and PSMA targeting specificity were identified in vitro and in vivo. With greatly enhanced tumor uptake and retention, [177Lu]Lu-LNC1003 has the potential to improve therapeutic efficacy using significantly lower dosages and less cycles of 177Lu that promises clinical translation to treat prostate cancer with various levels of PSMA expression.

Discovery of Novel Pentacyclic Triterpene Acid Amide Derivatives as Excellent Antimicrobial Agents Dependent on Generation of Reactive Oxygen Species.

Developing new agricultural bactericides is a feasible strategy for stopping the increase in the resistance of plant pathogenic bacteria. Some pentacyclic triterpene acid derivatives were elaborately designed and synthesized. In particular, compound A22 exhibited the best antimicrobial activity against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac) with EC50 values of 3.34 and 3.30 mg L-1, respectively. The antimicrobial mechanism showed that the compound A22 induced excessive production and accumulation of reactive oxygen species (ROS) in Xoo cells, leading to a decrease in superoxide dismutase and catalase enzyme activities and an increase in malondialdehyde content. A22 also produced increases in Xoo cell membrane permeability and eventual cell death. In addition, in vivo experiments showed that A22 at 200 mg L-1 exhibited protective activity against rice bacterial blight (50.44%) and citrus canker disease (84.37%). Therefore, this study provides a paradigm for the agricultural application of pentacyclic triterpene acid.

Fluoropolymer: A Review on Its Emulsion Preparation and Wettability to Solid-Liquid Interface.

In the preparation of a superamphiphobic surface, the most basic method is to reduce the surface free energy of the interface. The C-F bond has a very low surface free energy, which can significantly change the wettability of the solid-liquid interface and make it a hydrophobic or oleophobic, or even superamphiphobic surface. Based on the analysis of a large number of research articles, the preparation and application progress in fluoropolymer emulsion were summarized. After that, some corresponding thoughts were put forward combined with our professional characteristics. According to recent research, the status of the fluoropolymer emulsion preparation system was analyzed. In addition, all related aspects of fluoropolymer emulsion were systematically classified in varying degrees. Furthermore, the interaction between fluoropolymer structure and properties, especially the interaction with nanomaterials, was also explored. The aim of this review is to try to attract more scholars' attention to fluorocarbon interfacial materials. It is expected that it will make a certain theoretical and practical significance in the preparation and application of fluoropolymer.

Design, Synthesis and Bioactivity Evaluation of Novel 2-(pyrazol-4-yl)-1,3,4-oxadiazoles Containing an Imidazole Fragment as Antibacterial Agents.

Imidazole alkaloids, a common class of five-membered aromatic heterocyclic compounds, exist widely in plants, animals and marine organisms. Because of imidazole's extensive and excellent biological and pharmacological activities, it has always been a topic of major interest for researchers and has been widely used as an active moiety in search of bioactive molecules. To find more efficient antibacterial compounds, a series of novel imidazole-fragment-decorated 2-(pyrazol-4-yl)-1,3,4-oxadiazoles were designed and synthesized based on our previous works via the active substructure splicing principle, and their bioactivities were systematically evaluated both in vitro and in vivo. The bioassays showed that some of the target compounds displayed excellent in vitro antibacterial activity toward three virulent phytopathogenic bacteria, including Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Pseudomonas syringae pv. actinidiae (Psa), affording the lowest EC50 values of 7.40 (7c), 5.44 (9a) and 12.85 (9a) µg/mL, respectively. Meanwhile, compound 7c possessed good in vivo protective and curative activities to manage rice bacterial leaf blight at 200 µg/mL, with control efficacies of 47.34% and 41.18%, respectively. Furthermore, compound 9a showed commendable in vivo protective and curative activities to manage kiwifruit bacterial canker at 200 µg/mL, with control efficacies of 46.05% and 32.89%, respectively, which were much better than those of the commercial bactericide TC (31.58% and 17.11%, respectively). In addition, the antibacterial mechanism suggested that these new types of title compounds could negatively impact the cell membranes of phytopathogenic bacteria cells and cause the leakage of the intracellular component, thereby leading to the killing of bacteria. All these findings confirm that novel 2-(pyrazol-4-yl)-1,3,4-oxadiazoles containing an imidazole fragment are promising lead compounds for discovering new bactericidal agents.

An Improved Online Self-Calibration Method Utilizing Angular Velocity Observation for Ultra High Accuracy PIGA-Based IMU.

In the field of ultra high accuracy inertial measurement unit (IMU), pendulous integrating gyroscopic accelerometer (PIGA) has become a research hot spot due to its high-end performance. However, PIGA is sensitive to angular velocity, and the calibration process of PIGA-based IMU will be very complicated, which makes online self-calibration difficult to implement. To solve the above problems, we proposed an online self-calibration method utilizing angular velocity observation. The main contributions of this study are twofold: (1) An error analysis of PIGA is conducted in this paper, and the error model has also been simplified to suit the self-calibration model. (2) An improved online self-calibration method utilizing angular observation based on a simplified PIGA error model is proposed in this study. Experimental results show that the self-calibration method proposed in this study can improve the PIGA online calibration accuracy effectively (with the accuracy within 0.02 m/s/pulse), which can improve the dynamic accuracy of the PIGA.

The Discovery of Novel Ferulic Acid Derivatives Incorporating Substituted Isopropanolamine Moieties as Potential Tobacco Mosaic Virus Helicase Inhibitors.

Target-based drug design, a high-efficiency strategy used to guide the development of novel pesticide candidates, has attracted widespread attention. Herein, various natural-derived ferulic acid derivatives incorporating substituted isopropanolamine moieties were designed to target the tobacco mosaic virus (TMV) helicase. Bioassays demonstrating the optimized A19, A20, A29, and A31 displayed excellent in vivo antiviral curative abilities, affording corresponding EC50 values of 251.1, 336.2, 347.1, and 385.5 µg/mL, which visibly surpassed those of commercial ribavirin (655.0 µg/mL). Moreover, configurational analysis shows that the R-forms of target compounds were more beneficial to aggrandize antiviral profiles. Mechanism studies indicate that R-A19 had a strong affinity (Kd = 5.4 µM) to the TMV helicase and inhibited its ability to hydrolyze ATP (50.61% at 200 µM). Meanwhile, A19 could down-regulate the expression of the TMV helicase gene in the host to attenuate viral replication. These results illustrate the excellent inhibitory activity of A19 towards the TMV helicase. Additionally, docking simulations uncovered that R-A19 formed more hydrogen bonds with the TMV helicase in the binding pocket. Recent studies have unambiguously manifested that these designed derivatives could be considered as promising potential helicase-based inhibitors for plant disease control.

Novel aromatic sulfonyl naphthalene-based boronates as 20S proteasome inhibitors.

A novel series of non-peptide proteasome inhibitors (PIs) that act on chymotrypsin-like (ChT-L) of the proteasome were developed. These PIs bearing 4-aromatic sulfonyl naphthalene-based scaffold and Leu-boronic moiety as covalent bonding group displayed far better activity than PI-8182 for inhibiting ChT-L in preliminary biological activity test. The results showed that 2a (IC50 = 6.942 µM, MCF-7) and 2c (IC50 = 6.905 µM, MCF-7) displayed higher anti-proliferative activities than Bortezomib (IC50 = 18.37 µM, MCF-7) under our experimental conditions. Furthermore, in the microsomal stability assay, 2a demonstrated excellent metabolic stability profiles with 56% remaining after 40 min, as compared to Bortezomib of which approximately 30% was remaining. The compounds 2a, 2c emerged as promising lead compounds for the development of novel non-peptide boronate PIs.

Aggregated silver nanoparticles based surface-enhanced Raman scattering enzyme-linked immunosorbent assay for ultrasensitive detection of protein biomarkers and small molecules.

Lowering the detection limit is critical to the design of bioassays required for medical diagnostics, environmental monitoring, and food safety regulations. The current sensitivity of standard color-based analyte detection limits the further use of enzyme-linked immunosorbent assays (ELISAs) in research and clinical diagnoses. Here, we demonstrate a novel method that uses the Raman signal as the signal-generating system of an ELISA and combines surface-enhanced Raman scattering (SERS) with silver nanoparticles aggregation for ultrasensitive analyte detection. The enzyme label of the ELISA controls the dissolution of Raman reporter-labeled silver nanoparticles through hydrogen peroxide and generates a strong Raman signal when the analyte is present. Using this assay, prostate-specific antigen (PSA) and the adrenal stimulant ractopamine (Rac) were detected in whole serum and urine at the ultralow concentrations of 10(-9) and 10(-6) ng/mL, respectively. The methodology proposed here could potentially be applied to other molecules detection as well as PSA and Rac.

Rough surface Au@Ag core-shell nanoparticles to fabricating high sensitivity SERS immunochromatographic sensors.

Immunochromatographic sensors (ICSs) are inexpensive, simple, portable, and robust, thus making ICSs commonplace in clinical diagnoses, food testing, and environmental monitoring. However, commonly used gold nanoparticles (AuNPs) ICSs have low sensitivity. Therefore, we developed highly sensitive surface enhanced Raman scattering (SERS) ICSs. To enhance the sensitivity of SERS ICSs, rough surface core-shell Au@Ag nanoparticles (RSAu@AgNPs) were prepared by coating silver on the surface of gold nanoflowers (AuNFs). Then these nanoparticles were used as SERS substrate in the SERS ICSs, after which the SERS ICSs were implemented to detect haemoglobin and heavy metal cadmium ion (Cd(2+)). The limit of detection (LOD) of the SERS ICSs for detecting haemoglobin was 8 ng/mL, and the linear range of the SERS ICSs was from 31.3 to 2000 ng/mL. The LOD of the SERS ICSs for detecting Cd(2+) was 0.05 ng/mL and the linear analysis range was from 0.05 to 25 ng/mL. The cross reactivity of the SERS ICSs was studied and results showed that the SERS ICSs exhibited highly specific for detection of haemoglobin and Cd(2+), respectively. The SERS ICSs were then used to detect haemoglobin (spiked in serum and in stool) and Cd(2+) (spiked in tap water, river water, and soil leaching water), and the results showed high recovery. These characteristics indicated that SERS ICSs were ideal tools for clinical diagnosis and environmental pollution monitoring.

Silver nanoparticle enhanced Raman scattering-based lateral flow immunoassays for ultra-sensitive detection of the heavy metal chromium.

We report a simple and ultra-sensitive surface enhanced Raman scattering (SERS) strip sensor based on silver nanoparticles (AgNPs) and lateral flow immunoassays (LFIAs). LFIAs are inexpensive, simple, portable and robust, thus making them commonplace in medicine, agriculture and food safety. However, their applications are limited due to the low signal intensity of the color-formation reaction based on the label accumulation. SERS is a powerful molecular spectroscopy technique for ultra-detection, which is based on the enhancement of the inelastic scattering from molecules located near nanostructured metallic surfaces when the molecules are illuminated and the surface plasmons are excited. Because of the rapidity and robustness of LFIAs and the high sensitivity of SERS, we introduce SERS into LFIAs (SERS-LFIA). Our SERS-LFIA demonstrates fast, excellent performance and is suitable for the semiquantitative examination of ultratrace analytes (Cr(3+)), with the limit of the detection (LOD) as low as 10(-5) ng mL(-1), which is 10(5)-fold more highly sensitive than those previously used to detect Cr(3+) within 15 min.

Preparation and characterization of high-performance ceramic proppant from recycling utilization of oil-based drilling cuttings pyrolysis residues.

Oil-based drilling cutting pyrolysis residues (ODCPRs), bauxite, and sintering additives were applied to manufacture ceramic proppants with low density and high strength in this work. The effect of ODCPRs ratio, sintering temperature, holding time, and the content of additives on the performance of the proppants was comprehensively investigated, respectively. And the sintering mechanism of proppants was also discussed according to the phase, microstructure, and thermal behavior analyses. The results revealed that at the best sintering condition (1280 °C, holding for 60 min), and a mass ratio (ODCPRs: bauxite: MnO2 at 3:7:0.1), the well-developed granular corundum and acicular mullite formed inside the proppants and interspersed with each other to form a dense structure. The proppants presented low density and high strength as the bulk density of 1.48 g/cm3, the apparent density of 2.94 g/cm3, a breakage ratio of 5.25% under 52 MPa closed pressure, and the acid solubility of 4.80%, which could well meet the requirement of the standards of SY/T 5108-2014. This work provided a new pathway for recycling ODCPRs and the fabrication of high-performance proppants.

Development of Preladenant-Based Radiotracers for Imaging A2AR in Tumors.

Activation of the adenosine 2A receptor (A2AR) can lead to tumor immunosuppression, which results in poor prognosis of immunotherapy. The aim of this study was to design novel 18F-labeled probes ([18F]F-PFP2 and [18F]F-PFP4) to visualize A2AR in the tumor. The uptake of radioprobes in A2AR-negative 4T1 breast tumor was lower than that of A2AR-positive B16F10 melanoma at 1 h p.i. (1.22 ± 0.36% ID/g vs 2.80 ± 0.72% ID/g), 2 h p.i. (1.09 ± 0.20% ID/g vs 2.93 ± 0.76% ID/g) and 3 h p.i. (0.89 ± 0.27% ID/g vs 2.73 ± 0.58% ID/g), respectively. B16F10 lung metastasis models were employed to expand the application scenarios, observing significantly higher uptake of [18F]F-PFP2 in metastatic lesions compared to normal lung tissue (5.55 ± 2.18% ID/g vs 1.89 ± 0.65% ID/g, tumor/lung ratio ∼3). It is given that [18F]F-PFP2 might lay the foundation for establishing an A2AR-targeted imaging evaluation system for tumors, which will provide more precise guidance for personalized treatment.

A computed tomography-based radiomics nomogram for predicting overall survival in patients with connective tissue disease-associated interstitial lung disease.

OBJECTIVES: Accurate prognostic prediction is beneficial for the management of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The purpose of the present study was to develop and validate a nomogram using clinical features and computed tomography (CT) based radiomics features to predict overall survival (OS) in patients with CTD-ILD, and to assess the incremental prognostic value the radiomics might add to clinical risk factors. MATERIALS & METHODS: Patients from two clinical centers with CTD-ILD were enrolled in the present retrospective study. A radiomics signature, a clinical model and a combined nomogram were developed and assessed in the cohorts. The incremental value of radiomics signature to the clinical independent risk factors in survival prediction was evaluated. The models were externally validated to evaluate the model generalization ability. RESULTS: A total of 215 patients (mean age, 53 years ± 14 [standard deviation], 45 men) were evaluated. Patients with higher radiomics scores had higher mortality risk than those with lower radiomics scores (Hazard ratio, 12.396; 95% CI, 3.364-45.680; P < 0.001). The combined nomogram showed better predictive capability than the clinical model did with higher C-indices (0.800, 0.738, 0.742 vs. 0.747, 0.631, 0.587 in the training, internal- and external-validation cohort, respectively), time-AUCs and overall net-benefit. CONCLUSION: The radiomics signature is a potential prognostic biomarker of CTD-ILD and add incremental value to the clinical independent risk factors. The combined nomogram can provide a more accurate estimation of OS than the clinical model for CTD-ILD patients. CLINICAL RELEVANCE STATEMENT: The developed combined nomogram showed accurate prognostic prediction performance, which is beneficial for the management of CTD-ILD patients. It also proved radiomics could extract prognostic information from CT images.

Non-contrast computed tomography-based radiomics for staging of connective tissue disease-associated interstitial lung disease.

Rationale and introduction: It is of significance to assess the severity and predict the mortality of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). In this double-center retrospective study, we developed and validated a radiomics nomogram for clinical management by using the ILD-GAP (gender, age, and pulmonary physiology) index system. Materials and methods: Patients with CTD-ILD were staged using the ILD-GAP index system. A clinical factor model was built by demographics and CT features, and a radiomics signature was developed using radiomics features extracted from CT images. Combined with the radiomics signature and independent clinical factors, a radiomics nomogram was constructed and evaluated by the area under the curve (AUC) from receiver operating characteristic (ROC) analyses. The models were externally validated in dataset 2 to evaluate the model generalization ability using ROC analysis. Results: A total of 245 patients from two clinical centers (dataset 1, n = 202; dataset 2, n = 43) were screened. Pack-years of smoking, traction bronchiectasis, and nine radiomics features were used to build the radiomics nomogram, which showed favorable calibration and discrimination in the training cohort {AUC, 0.887 [95% confidence interval (CI): 0.827-0.940]}, the internal validation cohort [AUC, 0.885 (95% CI: 0.816-0.922)], and the external validation cohort [AUC, 0.85 (95% CI: 0.720-0.919)]. Decision curve analysis demonstrated that the nomogram outperformed the clinical factor model and radiomics signature in terms of clinical usefulness. Conclusion: The CT-based radiomics nomogram showed favorable efficacy in predicting individual ILD-GAP stages.

Discovery and Structural Optimization of 1,2,3,4-Tetrahydro-ß-carbolines as Novel Reactive Oxygen Species Inducers for Controlling Intractable Plant Bacterial Diseases.

Nowadays, reactive oxygen species (ROS) have been acknowledged as promising bactericidal targets against pesticide-resistant bacteria. Herein, to further excavate more excellent ROS inducers, simple 1,2,3,4-tetrahydro-ß-carboline derivatives containing a 3-aminopropanamide moiety were prepared and assessed for their antibacterial potency. Notably, three promising compounds displayed significant antibacterial potency. Compound I29 exhibits excellent in vitro bioactivity, with an EC50 value of 5.73 µg/mL, and admirable in vivo activities (protective activity of 55.74% and curative activity of 65.50%) toward Xanthomonas oryzae pv. oryzae. Compound I16 has good activity in vitro, with an EC50 of 3.43 µg/mL, and outstanding bioactivities in vivo (protective activity of 92.50% and curative activity of 59.68%) against Xanthomonas axonopodis pv. citri. Compound I6 shows excellent in vitro bioactivity (EC50 = 2.86 µg/mL) and significant protective activity (94.02%) for preventing Pseudomonas syringae pv. actinidiae. Antibacterial mechanism investigations indicate that these compounds disrupt the balance of the redox system to kill bacteria. These simple 1,2,3,4-tetrahydro-ß-carboline derivatives are promising leads to the discovery of bactericidal agents.

New Inspiration of 1,3,4-Oxadiazole Agrochemical Candidates: Manipulation of a Type III Secretion System-Induced Bacterial Starvation Mechanism to Prevent Plant Bacterial Diseases.

Discovering new anti-virulent agents to control plant bacterial diseases by preventing bacterial pathogenesis/pathogenicity rather than affecting bacterial growth is a sensible strategy. However, the effects of compound-manipulated bacterial virulence factors on host response are still not clear. In this work, 35 new 1,3,4-oxadiazole derivatives were synthesized and systematically evaluated for their anti-phytopathogenic activities. Bioassay results revealed that compound C7 possessed outstanding antibacterial activity in vitro (half-maximal effective concentration: 0.80 µg/mL) against Xanthomonas oryzae pv. oryzae (Xoo) and acceptable bioactivity in vivo toward rice bacterial leaf blight. Furthermore, virulence factor-related biochemical assays showed that C7 was a promising anti-virulent agent. Interestingly, C7 could indirectly reduce the inducible expression of host SWEET genes and thereby alleviate nutrient supply in the infection process of phytopathogenic bacteria. Our results highlight the potential of 1,3,4-oxadiazole-based agrochemicals for manipulating type III secretion system-induced phytopathogenic bacteria starvation mechanisms to prevent plant bacterial diseases.

Novel cinnamic acid derivatives as a versatile tool for developing agrochemicals for controlling plant virus and bacterial diseases by enhancing plant defense responses.

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.

Discovery of novel rost-4-ene derivatives as potential plant activators for preventing phytopathogenic bacterial infection: Design, synthesis and biological studies.

BACKGROUND: Gradually aggravated disease caused by phytopathogenic bacteria severely restricts food security and crop yield, and few pesticides can relieve this severe situation. Thus, development and excavation of new agrochemicals with high bioactivity and novel action mechanism may be a feasible strategy to control intractable bacterial diseases. As a privileged molecular framework, steroid molecules exhibit diversiform bioactivities. Herein, a series of novel androst-4-ene derivatives were designed, synthesised and investigated for their antibacterial behaviour to excavate novel agrochemicals on the base of steroid molecules. RESULTS: Bioassay results indicated that target compounds displayed high bioactivities toward three destructive phytopathogenic bacteria, including Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Pseudomonas syringae pv. actinidiae (Psa). Compound III19 displayed excellent in vitro antibacterial profiling (EC50  = 2.37 mg L-1 towards Xoo, EC50  = 2.10 mg L-1 towards Xac, EC50  = 9.50 mg L-1 towards Psa). Furthermore, compound III19 showed outstanding in vivo protective activities, with values of 81.81% and 58.75% towards kiwifruit bacterial canker and rice bacterial leaf blight, respectively. Analysis of the antibacterial mechanism disclosed that compound III19 enhanced host defence enzyme activities superoxide dismutase (SOD), peroxidase (POD), phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and catalase (CAT) and increased the salicylate synthase content to induce host resistance. In addition, compound III19 increased the membrane permeability, destroyed the cell membrane and killed the bacteria. CONCLUSION: Given these profiles of target compounds, we highlight a new strategy for controlling intractable plant bacterial diseases by inducing plant resistance and targeting the bacterial cell membrane. © 2022 Society of Chemical Industry.