A Novel Tryptanthrin Derivative D6 Induces Apoptosis and DNA Damage in Non-small-cell Lung Cancer Cells Through Regulating the EGFR Pathway.

BACKGROUND: Non-small-cell lung cancer is a prevalent malignancy associated with significant morbidity and mortality rates. Tryptanthrin and its derivatives have exhibited potent antitumor activity. OBJECTIVE: This study aims to investigate the inhibitory effect of a novel synthesized tryptanthrin derivative D6 on proliferation and the possible mechanism of human non-small cell lung cancer cell lines (A549) in vitro. METHODS: In this study, MTT assay, cell migration, colony formation assay, cell cycle analysis, cell apoptosis, JC- 1 staining assay, reactive oxygen species analysis, proteomics, western blotting, high content screening and absorption titrations analysis were performed. RESULTS: We found that D6 inhibited both the proliferation and migration, induced cell cycle arrest in the G2/M phase, increased levels of ROS, decreased mitochondrial membrane potential, and promoted apoptosis in A549 cells. Further mechanistic studies found that D6 reduced EGFR expression in A549 cells and inhibited the EGFR pathway by decreasing phosphorylation levels of EGFR, Stat3, AKT and Erk1/2. Moreover, DNA damage induced by D6 involved an increase in p53/MDM2 ratio and concentration-dependent accumulation of micronuclei. CONCLUSION: D6 demonstrated significant antitumor activity against A549 cells by inhibiting the EGFR signaling pathway, inducing DNA damage, and subsequently leading to oxidative stress, apoptosis, and cell cycle arrest. Our findings suggest that D6 exhibits potential as an NSCLC drug, owing to its attributes such as antiproliferative activity and ability to induce apoptosis by attenuating the EGFR-mediated signaling pathway.

Moderate cryptoxanthin intake correlates with maintenance of a proper PINT index in a general Japanese population.

INTRODUCTION: Small fibre neuropathy (SFN) is an early manifestation of diabetic polyneuropathy. Although oxidative stress, inflammation and change of intestinal bacterial population are assumed to be their pathogenesis, the effects of dietary nutrition have not been evaluated. The relationship between dietary nutrition intake and pain sensation was evaluated in the Japanese population. METHODS: We conducted the Iwaki project, a population-based study recruiting 1,028 individuals, in 2018. The relationships between the pain threshold from intraepidermal electrical stimulation (PINT) and the amount of dietary nutrition evaluated by a brief-type self-administered diet history questionnaire were examined. The odds ratio was further explored after categorizing subjects based on low (< 63.7 µg/day), intermediate (63.7-159.2 µg/day), and high cryptoxanthin levels (> 159.2 µg/day). RESULTS: Univariate linear regression analyses showed significant correlations between PINT and cryptoxanthin intake even after adjustments for other nutritional intakes (ß = 0.107, p < 0.01). Multivariate logistic regression analysis revealed low and high cryptoxanthin intake as significant risk factors for abnormal PINT (≥ 0.20 mA). Multivariate linear regression analyses showed significant correlations between PINT and cryptoxanthin intake levels after adjustment for other clinically PINT-related factors (ß = 0.09, p < 0.01). CONCLUSIONS: Adequate intake of cryptoxanthin is recommended to maintain the pain threshold in the Japanese population.

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.

Antifungal Activity of Novel Indole Derivatives Containing 1,3,4-Thiadiazole.

In this study, 24 indole derivatives containing 1,3,4-thiadiazole were discovered and synthesized. The target compounds' antifungal efficacy against 14 plant pathogenic fungal pathogens was then determined in vitro. With an EC50 value of 2.7 µg/mL, Z2 demonstrated the highest level of bioactivity among them against Botrytis cinerea (B.c.), exceeding the concentrations of the control prescription drugs azoxystrobin (Az) (EC50 = 14.5 µg/mL) and fluopyram (Fl) (EC50 = 10.1 µg/mL). Z2 underwent in vivo testing on blueberry leaves in order to evaluate its usefulness in real-world settings. A reasonable protective effect was obtained with a control effectiveness of 93.0% at 200 µg/mL, which was superior to those of Az (83.0%) and Fl (52.0%). At 200 µg/mL, this chemical had an efficacy of 84.0% in terms of curative efficacy. These figures outperformed those of Az (69.0%) and Fl (48.0%). Scanning electron microscopy (SEM) experiments and light microscopy experiments showed that Z2 altered the integrity of the cell wall and cell membrane of the pathogenic fungus B.c., which led to an increase in the content of malondialdehyde (MDA), cellular leakage, and cellular permeability. Enzyme activity assays and molecular docking studies indicated that Z2 could act as a potential succinate dehydrogenase inhibitor (SDHI). It was hypothesized that Z2 could cause disruption of mycelial cell membranes, which in turn leads to mycelial death. According to the research, indole derivatives containing 1,3,4-thiadiazole were expected to evolve into new fungicides due to their significant antifungal effects on plant fungi.

Tryptophan metabolism and small fibre neuropathy: a correlation study.

Small nerve fibres located in the epidermis sense pain. Dysfunction of these fibres decreases the pain threshold known as small fibre neuropathy. Diabetes mellitus is accompanied by metabolic changes other than glucose, synergistically eliciting small fibre neuropathy. These findings suggest that various metabolic changes may be involved in small fibre neuropathy. Herein, we explored the correlation between pain sensation and changes in plasma metabolites in healthy Japanese subjects. The pain threshold evaluated from the intraepidermal electrical stimulation was used to quantify pain sensation in a total of 1021 individuals in the 2017 Iwaki Health Promotion Project. Participants with a pain threshold evaluated from the intraepidermal electrical stimulation index <0.20 mA were categorized into the pain threshold evaluated from the intraepidermal electrical stimulation index-low group (n = 751); otherwise, they were categorized into the pain threshold evaluated from the intraepidermal electrical stimulation index-high group (n = 270). Metabolome analysis of plasma was conducted using capillary electrophoresis time-of-flight mass spectrometry. The metabolite set enrichment analysis revealed that the metabolism of tryptophan was significantly correlated with the pain threshold evaluated from the intraepidermal electrical stimulation index in all participants (P < 0.05). The normalized level of tryptophan was significantly decreased in participants with a high pain threshold evaluated from the intraepidermal electrical stimulation index. In addition to univariate linear regression analyses, the correlation between tryptophan concentration and the pain threshold evaluated from the intraepidermal electrical stimulation index remained significant after adjustment for multiple factors (ß = -0.07615, P < 0.05). These findings indicate that specific metabolic changes are involved in the deterioration of pain thresholds. Here, we show that abnormal tryptophan metabolism is significantly correlated with an elevated pain threshold evaluated from the intraepidermal electrical stimulation index in the Japanese population. This correlation provides insight into the pathology and clinical application of small fibre neuropathy.

Tryptanthrin Derivative B1 Binds Viral Genome-Linked Protein (VPg) of Potato Virus Y.

Potato virus Y (PVY) is a plant virus that is known to be responsible for substantial economic losses in agriculture. Within the PVY genome, viral genome-linked protein (VPg) plays a pivotal role in the viral translation process. In this study, VPg was used as a potential target for analyzing the antiviral activity of tryptanthrin derivatives. In vitro, the dissociation constants of B1 with PVY VPg were 0.69 µmol/L (measured by microscale thermophoresis) and 4.01 µmol/L (measured via isothermal titration calorimetry). B1 also strongly bound to VPg proteins from three other Potyviruses. Moreover, in vivo experiments demonstrated that B1 effectively suppressed the expression of the PVY gene. Molecular docking experiments revealed that B1 formed a hydrogen bond with N121 and that no specific binding occurred between B1 and the PVY VPgN121A mutant. Therefore, N121 is a key amino acid residue in PVY VPg involved in B1 binding. These results highlight the potential of PVY VPg as a potential target for the development of antiviral agents.

Design, synthesis, antibacterial evaluation of isopropylamine linked with different substituted phenol and piperazine novel derivatives.

BACKGROUND: Xanthomonas oryzae pv. oryzae (Xoo) is often considered one of the most destructive bacterial pathogens causing bacterial leaf blight (BLB), resulting in significant yield and cost losses in rice. In this study, a series of novel derivatives containing the isopropanolamine moiety linked to various substituted phenols and piperazines were designed, synthesized and screened. RESULTS: Antibacterial activity results showed that most compounds had good inhibitory effects on Xoo, among which compound W2 (EC50 = 2.74 µg mL-1) exhibited the most excellent inhibitory activity, and W2 also had a certain curative effect (35.89%) on rice compared to thiodiazole copper (TC) (21.57%). Scanning electron microscopy (SEM) results indicated that compound W2 could cause rupture of the Xoo cell membrane. Subsequently, proteomics and quantitative real-time polymerase chain reaction revealed that compound W2 affected the physiological processes of Xoo and may exert antibacterial activity by targeting the two-component system pathway. Interestingly, W2 upregulated Xoo's methyltransferase to impact on its pathogenicity. CONCLUSION: The present study offers a promising phenolic-piperazine-sopropanolamine compound as an innovative antibacterial strategy by specifically targeting the two-component system pathway and inducing upregulation of methyltransferase to effectively impact Xoo's pathogenicity. © 2024 Society of Chemical Industry.

Diabetes can increase the prevalence of EBV infection and worsen the prognosis of nasopharyngeal carcinoma.

Epstein‒Barr virus (EBV) infection is a primary oncogenic factor of nasopharyngeal carcinoma (NPC) that elicits epithelial-mesenchymal transition (EMT). Although diabetic patients are more susceptible to various infectious diseases, the pathological association with virus-related NPC has not yet been clarified. Herein, we evaluated the influence of diabetes on the clinicopathological changes of 70 patients with NPC. Disease-specific survival (DSS) modified by viral infection was also analysed. The proportion of NPC patients with diabetes was 32.9% (23/70 cases), and 91.3% (21/23 cases) were infected with EBV detected by EBER-I in situ hybridisation. NPC with diabetes showed an effect on EMT evaluated by immunostaining for E-cadherin and vimentin, which was correlated with HbA1c levels. Receiver operating characteristic (ROC) curve analysis determined a HbA1c level of 6.5% as the cut-off value for primary disease death at 2 years [area under the curve (AUC) 0.76; sensitivity 0.64; and specificity 0.81]. High HbA1c levels (≥6.5%) significantly increased the number of lymph node metastases in NPC compared to low HbA1c levels (<6.5%, p<0.01). Diabetic NPC patients had a significantly poorer prognosis than all non-diabetic patients (DSS, 72 months vs not reached, p<0.05). Diabetic EBV-positive NPC patients had a significantly poorer prognosis than non-diabetic EBV-positive patients (DSS, 35 months vs not reached, p<0.01). Multivariate analysis using the Cox proportional hazards model also suggested that HbA1c ≥6.5% was a significant factor in poor prognosis, with a hazard ratio of 6.84 (p<0.05). Collectively, our results revealed for the first time a high prevalence of EBV infection, poor prognosis and the importance of proper glycaemic control in diabetic NPC patients.

Discovery of tryptanthrin analogues bearing F and piperazine moieties as novel phytopathogenic antibacterial and antiviral agents.

BACKGROUND: Plant bacterial infections and plant viruses seriously affect the yield and quality of crops. Based on the various activities of tryptanthrin, a series of tryptanthrin analogues bearing F and piperazine moieties were designed, synthesized, and evaluated for their biological activities against three plant bacteria and tobacco mosaic virus (TMV). RESULTS: Bioassay results indicated that compounds 6a-6l displayed excellent antibacterial activities in vitro and 6a-6c and 6g exhibited better antiviral activities against TMV than commercial ribavirin. In particular, 6b showed the most effect on Xanthomonas oryzae pv. oryzae (Xoo) with a half-maximal effective concentration (EC50 ) of 1.26 µg mL-1 , compared with the commercial pesticide bismerthiazol (BT; EC50 = 34.3 µg mL-1 ) and thiodiazole copper (TC; EC50 = 73.3 µg mL-1 ). Meanwhile, 6a also had the best antiviral activity at 500 µg mL-1 for curative, protection, and inactivation purposes, compared with ribavirin in vivo. CONCLUSION: Compound 6b could cause changes in bacterial morphology, induce the accumulation of reactive oxygen species, promote apoptosis of bacterial cells, inhibit the formation of biofilm, and block the growth of Xoo cells. Proteomic analysis revealed major differences in the bacterial secretory system pathways T2SS and T6SS, which inhibited membrane transport. Molecular docking revealed that 6a and 6g could interact with TMV coat protein preventing virus assembly. These results suggest that tryptanthrin analogues bearing F and piperazine moieties could be promising candidate agents for antibacterial and antiviral use in agricultural production. © 2023 Society of Chemical Industry.

P7C3-A20 treats traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.

Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain. 3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine (P7C3-A20) can be neuroprotective in various diseases, including ischemic stroke and neurodegenerative diseases. However, whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear. Therefore, in the present study, we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms. We established a traumatic brain injury rat model using a modified weight drop method. P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury. Severe neurological deficits were found in rats after traumatic brain injury, with deterioration in balance, walking function, and learning memory. Furthermore, hematoxylin and eosin staining showed significant neuronal cell damage, while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis. The presence of autolysosomes was observed using transmission electron microscope. P7C3-A20 treatment reversed these pathological features. Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-II (LC3-II) autophagy protein, apoptosis-related proteins (namely, Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 [BNIP3], and Bcl-2 associated x protein [Bax]), and elevated ubiquitin-binding protein p62 (p62) autophagy protein expression. Thus, P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.

Design, Synthesis, and Mechanism of Novel 9-Aliphatic Amine Tryptanthrin Derivatives against Phytopathogenic Bacteria.

Taking inspiration from the use of natural product-derived bactericide candidates in drug discovery, a series of novel 9-aliphatic amine tryptanthrin derivatives were designed, synthesized, and evaluated for their biological activity against three plant bacteria. The majority of these compounds exhibited excellent antibacterial activity in vitro. Compound 7c exhibited a significantly superior bacteriostatic effect against Xanthomonas axonopodis pv Citri (Xac), Xanthomonas oryzae pv Oryzae (Xoo), and Pseudomonas syringae pv Actinidiae (Psa) with final corrected EC50 values of 0.769, 1.29, and 15.5 µg/mL, respectively, compared to the commercial pesticide thiodiazole copper which had EC50 values of 58.8, 70.9, and 91.9 µg/mL. Preliminary mechanism studies have demonstrated that 7c is capable of altering bacterial morphology, inducing reactive oxygen species accumulation, promoting bacterial cell apoptosis, inhibiting normal cell growth, and affecting cell membrane permeability. Moreover, in vivo experiments have substantiated the effectiveness of 7c as a therapeutic and defensive agent against the citrus canker. The proteomic analysis has unveiled that the major disparities are located within the bacterial secretion system pathway, which hinders membrane transportation. These discoveries imply that 7c could be an auspicious prototype for developing antiphytopathogenic bacterial agents.

Discovery and Mechanism of Novel 7-Aliphatic Amine Tryptanthrin Derivatives against Phytopathogenic Bacteria.

Rice bacterial leaf blight is a destructive bacterial disease caused by Xanthomonas oryzae pv. oryzae (Xoo) that seriously threatens crop yields and their associated economic benefits. In this study, a series of improved dissolubility 7-aliphatic amine tryptanthrin derivatives was designed and synthesized, and their potency in antibacterial applications was investigated. Notably, compound 6e exhibited excellent activity against Xoo, with an EC50 value of 2.55 µg/mL, compared with the positive control bismerthiazol (EC50 = 35.0 µg/mL) and thiodiazole copper (EC50 = 79.4 µg/mL). In vivo assays demonstrated that 6e exhibited a significant protective effect on rice leaves. After exposure, the morphology of the bacteria was partially atrophied by SEM. Furthermore, 6e increased the accumulation of intracellular reactive oxygen species, causing cell apoptosis and the formation of bacterial biofilms. All the results indicated that 6e could be a potential agrochemical bactericide for controlling phytopathogenic bacteria.

Design, Synthesis and Antitumor Activity of 1H-indazole-3-amine Derivatives.

A series of indazole derivatives were designed and synthesized by molecular hybridization strategy, and these compounds were evaluated the inhibitory activities against human cancer cell lines of lung (A549), chronic myeloid leukemia (K562), prostate (PC-3), and hepatoma (Hep-G2) by methyl thiazolyl tetrazolium (MTT) colorimetric assay. Among these, compound 6o exhibited a promising inhibitory effect against the K562 cell line with the IC50 (50% inhibition concentration) value of 5.15 µM, and this compound showed great selectivity for normal cell (HEK-293, IC50 = 33.2 µM). Moreover, compound 6o was confirmed to affect apoptosis and cell cycle possibly by inhibiting Bcl2 family members and the p53/MDM2 pathway in a concentration-dependent manner. Overall, this study indicates that compound 6o could be a promising scaffold to develop an effective and low-toxic anticancer agent.

Discovery and Mechanism of Azatryptanthrin Derivatives as Novel Anti-Phytopathogenic Bacterial Agents for Potent Bactericide Candidates.

The natural alkaloids of tryptanthrin and their derivatives have a wide range of biological activities. In this research, four series of azatryptanthrin derivatives containing 4-aza/3-aza/2-aza/1-aza tryptanthrin were prepared by condensation cyclization reaction against plant pathogens to develop a new natural product-based bacterial pesticide. Compound 4Aza-8 displayed a remarkable growth inhibitory effect on pathogenic bacteria of Xanthomonas axonopodis pv. citri (Xac), Xanthomonas oryzae pv. Oryzae (Xoo), and Pseudomonas syringae pv. actinidiae (Psa) with the final corrected EC50 values of 0.312, 1.91, and 18.0 µg/mL, respectively, which were greatly superior than that of tryptanthrin (Tryp). Moreover, 4Aza-8 also showed effective therapeutic and protective activities in vivo on citrus canker. Further mechanism studies on Xac elucidated that compound 4Aza-8 was able to affect the growth curve of Xac and the formation of biofilm, cause severe shrinkage in bacterial morphology, increase reactive oxygen species levels, and induce apoptosis in bacterial cells. Quantitative analysis of differential protein profiles found that the major differences were mainly concentrated on the endometrial protein in the bacterial secretion system pathway, which blocked the membrane transport and affected the transfer of DNA to the host cell. In summary, these research results suggest that 4Aza-8 represents a promising anti-phytopathogenic-bacteria agent, which is worth being further investigated as a bactericide candidate.

Design, Synthesis, Antibacterial Evaluation, Three-Dimensional Quantitative Structure-Activity Relationship, and Mechanism of Novel Quinazolinone Derivatives.

Plant bacterial illnesses are common and cause dramatic damage to agricultural goods all over the world, yet there are few efficient bactericides to alleviate them at present. To discover novel antibacterial agents, two series of quinazolinone derivatives with novel structures were synthesized and their bioactivity against plant bacteria was tested. Combining CoMFA model search and the antibacterial bioactivity assay, D32 was identified as a potent antibacterial inhibitor against Xanthomonas oryzae pv. Oryzae (Xoo), with an EC50 value of 1.5 µg/mL, much better in inhibitory capacity compared to bismerthiazol (BT) and thiodiazole copper (TC) (31.9 and 74.2 µg/mL). The activities of compound D32 against rice bacterial leaf blight in vivo were 46.7% (protective activities) and 43.9% (curative activities), better than commercial drug thiodiazole copper (29.3% protective activities and 30.6% curative activities). Flow cytometry, proteomics, reactive oxygen species, and key defense enzymes were used to further investigate the relevant mechanisms of action of D32. The identification of D32 as an antibacterial inhibitor and revelation of its recognition mechanism not only open the possibility of developing new therapeutic strategies for treatment of Xoo but also provide clues for elucidation of the acting mechanism of quinazolinone derivative D32, which is a possible clinical candidate worth in-depth study.

Discovery of Tryptanthrin and Its Derivatives and Its Activities against NSCLC In Vitro via Both Apoptosis and Autophagy Pathways.

In this study, a series of novel tryptanthrin derivatives were synthesized and their inhibitory activities against selected human cancer cell lines, namely, lung (A549), chronic myeloid leukemia (K562), prostate (PC3), and live (HepG2), were evaluated using a methyl thiazolyl tetrazolium colorimetric (MTT) assay. Among the tested compounds, compound C1 exhibited a promising inhibitory effect on the A549 cell line with an IC50 value of 0.55 ± 0.33 µM. The observation of the cell morphological result showed that treatment with C1 could significantly inhibit the migration of A549 cells through the cell migration assay. Moreover, after treatment with C1, the A549 cells exhibited a typical apoptotic morphology and obvious autophagy. In addition, the detection of apoptosis and the mitochondrial membrane potential indicated that C1 induced A549 cell apoptosis via modulating the levels of Bcl2 family members and disrupted the mitochondrial membrane potential. Compound C1 also suppressed the expression of cyclin D1 and increased the expression of p21 in the A549 cells, inducing cell cycle arrest in the G2/M phase in a dose dependent manner. The further mechanism study found that C1 markedly increased the transformation from LC3-I to LC3-II. Taken together, our results suggest that C1 is capable of inhibiting the proliferation of non-small cell lung cancer (NSCLC) cells, inducing cell apoptosis, and triggering autophagy.

Synthesis and biological assessment of indole derivatives containing penta-heterocycles scaffold as novel anticancer agents towards A549 and K562 cells.

Herein, a new series of 2-chloro-N-(5-(2-oxoindolin-3-yl)-4H-pyrazol-3-yl) acetamide derivatives containing 1,3,4-thiadiazole (10a-i) and 4H-1,2,4-triazol-4-amine (11a-r) moiety was designed, synthesised as novel anticancer agents. The antiproliferative activity values indicated that compound 10 b stood as the most potent derivative with IC50 values of 12.0 nM and 10 nM against A549 and K562 cells, respectively. Mechanism investigation and docking studies of 10 b indicated that it possessed good apoptosis characteristic and dose-dependent growth arrest of A549 and K562 cells, blocked cell cycle into G2/M phase. Interestingly, 10 b suppressed the growth of A549 and K562 cells via modulation of EGFR and p53-MDM2 mediated pathway.

Cysteine protease domain of potato virus Y: The potential target for urea derivatives.

The cysteine protease structural domain (CPD) encoded by the potato virus Y (PVY) accessory component protein helper component-proteinase (HC-Pro) is an auxiliary component of aphid virus transmission and plays an important role in virus infection and replication. Urea derivatives have potential antiviral activities. In this study, the PVY HC-Pro C-terminal truncated recombinant protein (residues 307-465) was expressed and purified. The interactions of PVY CPD with urea derivatives HD1-36 were investigated. Microscale thermophoresis experiments showed that HD6, -19, -21 and - 25 had the strongest binding forces to proteins, with Kd values of 2.16, 1.40, 1.97 and 1.12 µM, respectively. An experiment verified the microscale thermophoresis results, and the results were as expected, with Kd values of 6.10, 4.78, 5.32, and 4.52 µM for HD6, -19, -21, and - 25, respectively. Molecular docking studies indicated that the interaction sites between PVY CPD and HD6, -19, -21, and - 25, independently, were aspartic acid 121, asparagine 48, and tyrosine 38, which played important roles in their binding. In vivo experiments verified that HD25 inhibited PVY more than the control agents ningnanmycin and urea. These data have important implications for the design and synthesis of novel urea derivatives.

Allicin-inspired disulfide derivatives containing quinazolin-4(3H)-one as a bacteriostat against Xanthomonas oryzae pv. oryzae.

BACKGROUND: Plant bacterial diseases have seriously affected the yield and quality of crops, among which rice bacterial leaf blight (BLB), caused by Xanthomonas oryzae pv. oryzae has seriously affected the yield of rice. As plant-pathogenic bacteria gradually become resistant to existing bactericides, it is necessary to find effective bactericides with novel structures. RESULTS: Herein, a series of compounds containing quinazolin-4(3H)-one and disulfide moieties were designed and synthesized using a facile synthetic method. The bioassay results revealed that most target compounds possessed noticeable antibacterial activity against Xanthomonas oryzae pv. oryzae. Particularly, compound 2-(butyldisulfanyl) quinazolin-4(3H)-one (1) exhibited remarkable antibacterial activity with the half effective concentration (EC50 ) of 0.52 µg mL-1 . Additionally, compound 1 was confirmed to inhibit the growth of the bacteria, change the bacterial morphology, and increase the level of reactive oxygen species. Proteomics, and RT-qPCR analysis results indicated that compound 1 could downregulate the expression of Pil-Chp histidine kinase chpA encoded by the pilL gene, and the potting experiments proved that compound 1 exhibits significant protective activity against BLB. CONCLUSIONS: Compound 1 may weaken the pathogenicity of Xanthomonas oryzae pv. oryzae by inhibiting the bacterial growth and blocking the pili-mediated twitching motility without inducing the bacterial apoptosis. This study indicates that such derivatives could be a promising scaffold to develop a bacteriostat to control BLB. © 2022 Society of Chemical Industry.

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.