Floro-pyrazolo[3,4-d]pyrimidine derivative as a novel plant activator induces two-pathway immune system

Shi, Qinjie; Ji, Yuanyuan; Shi, Yanhong; Zhao, Zhenjiang; Zhu, Weiping; Xu, Yufang; Li, Baoju; Qian, Xuhong

doi:10.1016/j.phytochem.2021.112657

Cited by 8 publications

(5 citation statements)

References 33 publications

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“…Pro-inflammatory signaling is linked to Th1* cells in rheumatoid arthritis, multiple sclerosis, and Crohn’s disease. This specific subset of cells plays a crucial role in the defense against infection and the management of autoimmunity and inflammation ( 43 ). Previous research has focused on the transcriptome of immunological hallmark genes in human Th1* cells.…”

Section: Discussionmentioning

confidence: 99%

Pyrimidine metabolism regulator-mediated molecular subtypes display tumor microenvironmental hallmarks and assist precision treatment in bladder cancer

Wu,

Li,

et al. 2023

Front. Oncol.

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BackgroundBladder cancer (BLCA) is a common urinary system malignancy with a significant morbidity and death rate worldwide. Non-muscle invasive BLCA accounts for over 75% of all BLCA cases. The imbalance of tumor metabolic pathways is associated with tumor formation and proliferation. Pyrimidine metabolism (PyM) is a complex enzyme network that incorporates nucleoside salvage, de novo nucleotide synthesis, and catalytic pyrimidine degradation. Metabolic reprogramming is linked to clinical prognosis in several types of cancer. However, the role of pyrimidine metabolism Genes (PyMGs) in the BLCA-fighting process remains poorly understood.MethodsPredictive PyMGs were quantified in BLCA samples from the TCGA and GEO datasets. TCGA and GEO provided information on stemness indices (mRNAsi), gene mutations, CNV, TMB, and corresponding clinical features. The prediction model was built using Lasso regression. Co-expression analysis was conducted to investigate the relationship between gene expression and PyM.ResultsPyMGs were overexpressed in the high-risk sample in the absence of other clinical symptoms, demonstrating their predictive potential for BLCA outcome. Immunological and tumor-related pathways were identified in the high-risk group by GSWA. Immune function and m6a gene expression varied significantly between the risk groups. In BLCA patients, DSG1, C6orf15, SOST, SPRR2A, SERPINB7, MYBPH, and KRT1 may participate in the oncology process. Immunological function and m6a gene expression differed significantly between the two groups. The prognostic model, CNVs, single nucleotide polymorphism (SNP), and drug sensitivity all showed significant gene connections.ConclusionsBLCA-associated PyMGs are available to provide guidance in the prognostic and immunological setting and give evidence for the formulation of PyM-related molecularly targeted treatments. PyMGs and their interactions with immune cells in BLCA may serve as therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Pyrimidine metabolism regulator-mediated molecular subtypes display tumor microenvironmental hallmarks and assist precision treatment in bladder cancer

Wu,

Li,

et al. 2023

Front. Oncol.

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“…In contrast to INA-and BTH-mediated immunity, which are exclusively dependent on the transcriptional cofactor and SA coreceptor NPR1 [9], DCAmediated immunity is only weakly dependent on NPR1 and partially dependent on the signaling pathway of the WRKY70 transcription factor [30]. Floro-pyrazolo [3,4-d]pyrimidine derivative as a novel plant activator induces SAR and induced systemic resistance (ISR) pathways that can highly induce resistance to plant pathogens [33]. In this study, LY5-24-2, as a plant immune activator candidate, was identified as partially dependent on the NPR1mediated SA signaling pathway to enhance resistance to Hpa in Arabidopsis.…”

Section: Discussionmentioning

confidence: 99%

Plant Defense Responses to a Novel Plant Elicitor Candidate LY5-24-2

Chen

et al. 2022

IJMS

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Plant elicitors enhance plant defense against pathogen attacks by inducing systemic acquired resistance (SAR) with no or low direct fungicidal activity. Here we report the synthesis of a novel plant elicitor candidate LY5-24-2 [3,4-dichloro-N-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)isothiazole-5-carboxamide] and evaluation of its SAR inducing activity. Bioassays indicated that LY5-24-2 did not show significant anti-fungal activity but provided long-lasting resistance in Arabidopsis thaliana (A. thaliana) through promoting the accumulation of lignin, cellulose and pectin by 60.1%, 82.4% and 305.6%, respectively, at a concentration of 100 µM. LY5-24-2 also facilitated the closure of leaf stomata and increased the intracellular free Ca2+ by 47.8%, induced reactive oxygen species (ROS) accumulation, and inhibited the activity of ascorbate peroxidase (APX, EC 1.11.1.11) and catalase (CAT, EC 1.11.1.6) by 38.9% and 34.0%, respectively, as compared with the control at a concentration of 100 µM. LY5-24-2 induced SAR in plants and was dependent on the NPR1-mediated SA pathway by up-regulating expression of 2273 genes in A. thaliana. Meanwhile, LY5-24-2 also improved cucumber (Cucumis sativus L.) defense against Pseudoperonospora cubensis (P. cubensis) through promoting ROS accumulation and inhibiting activity of APX and CAT by 30.7% and 23.1%, respectively. Its expression of SA signaling genes CsNPR1, CsPR4 and CsPR5 was enhanced by 10.8, 5.8 and 6.6 times, respectively. These results demonstrated that LY5-24-2 is a novel elicitor candidate for plant protection via inducing SAR.

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“…3,4 Pyrimidine heterocyclic compounds have been widely used as active pharmacophores in the field of medicine and pesticides. 4,5 Many of their substituted derivatives, including thieno [3,2-d] pyrimidines as Tpl2 kinase inhibitors, can inhibit tumors and inflammatory diseases. 6 Thieno [2,3-d]pyrimidinedione is an antibacterial agent that inhibits a variety of gram-positive and gramnegative bacteria.…”

Section: Introductionmentioning

confidence: 99%

“…Pyrimidine heterocyclic compounds have been widely used as active pharmacophores in the field of medicine and pesticides 4,5 . Many of their substituted derivatives, including thieno[3,2‐d]pyrimidines as Tpl2 kinase inhibitors, can inhibit tumors and inflammatory diseases 6 .…”

Section: Introductionmentioning

confidence: 99%

Antiviral modes of action of the novel compound GLY‐15 containing pyrimidine heterocycle and moroxydine skeleton against tobacco mosaic virus

Guo

et al. 2022

Pest Management Science

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BACKGROUND Plant virus diseases are difficult to prevent and control, causing serious economic losses to the agricultural production world. To develop new pesticides with antiviral activity, a serial of compounds containing the structure of pyrimidine and moroxydine were synthesized, among which GLY‐15 exhibited good antiviral activity against tobacco mosaic virus (TMV), while the mechanism of antiviral activity remains to be clarified. RESULTS GLY‐15 treatment significantly inhibited the formation of necrotic spots caused by TMV in Nicotiana glutinosa, and effectively suppressed the systemic transportation of TMV expressing a reporter gene (p35S‐30B:GFP) in N. benthamiana and markedly reduced the accumulation of a movement deficient TMV in plants as well as viral RNA accumulation in tobacco protoplasts. The results of RNA sequencing showed that GLY‐15 induced significant differential expression of genes or pathways involved in the stress response, defense response and signal transduction, phytohormone response and metabolism. Among them, real‐time quantitative PCR validated that the expression of 12 critical genes such as heat shock protein, receptor kinase, cell‐wall‐related protein, disease‐related protein and glucan endo‐1,3‐β‐glucosidase were significantly up‐regulated. In addition, GLY‐15 triggered reactive oxygen species (ROS) production and induced the activity of several crucial defense related enzymes in plants. The results of molecular docking showed potential binding ability of GLY‐15 with TMV helicase and the coat protein. CONCLUSION This study provide valuable insights into antiviral mechanism of action for GLY‐15, which is expected to be applied as a pesticide for the management of plant viruses. © 2022 Society of Chemical Industry.

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Floro-pyrazolo[3,4-d]pyrimidine derivative as a novel plant activator induces two-pathway immune system

Cited by 8 publications

References 33 publications

Pyrimidine metabolism regulator-mediated molecular subtypes display tumor microenvironmental hallmarks and assist precision treatment in bladder cancer

Pyrimidine metabolism regulator-mediated molecular subtypes display tumor microenvironmental hallmarks and assist precision treatment in bladder cancer

Plant Defense Responses to a Novel Plant Elicitor Candidate LY5-24-2

Antiviral modes of action of the novel compound GLY‐15 containing pyrimidine heterocycle and moroxydine skeleton against tobacco mosaic virus

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