Specific inhibition effects of N -pentafluorobenzyl-1-deoxynojirimycin on human CD4+ T cells

Zhang, Xiaolian; Liu, Min; Xie, Peng; Wan, Shuhui; Ye, Jia Tao; Zhou, Xiang; Wu, Jing

doi:10.1016/j.bmcl.2004.04.092

Cited by 10 publications

(5 citation statements)

References 11 publications

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“…[33] It was found that 5F-DNJ, much less toxic than CyA, remarkably inhibited the secretion of IL-4 and had a specific inhibition on the expression of CD4 molecules. Furthermore, 5F-DNJ not only markedly inhibited in vitro IL-4 production from human PBMCs, CD4 + T cells, and mouse splenocytes, but also strongly inhibited the production of IL-4 in splenocytes from a mouse model of S. japonicum infection.…”

Section: And6mentioning

confidence: 98%

Iminosugars as Immunomodulating Agents: Synthesis and Biological Activities of 1‐Deoxynojirimycin and Related Compounds

Qin

2015

Israel Journal of Chemistry

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Iminosugars are an extremely interesting and versatile class of compounds and have many potential therapeutic applications. However, the use of iminosugar derivatives as immunomodulating agents is an area that is less explored. This review describes recent advances in the field of iminosugars as immunomodulating agents with a particular emphasis on 1‐deoxynojirimycin analogues and related compounds. Both chemical and biological aspects concerning their preparation and/or occurrence in nature, as well as their immunomodulatory properties, are discussed.

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Section: And6mentioning

confidence: 98%

Iminosugars as Immunomodulating Agents: Synthesis and Biological Activities of 1‐Deoxynojirimycin and Related Compounds

Qin

2015

Israel Journal of Chemistry

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“…Human CD4 molecules have two Nglycosylation sites, while mouse CD4 molecules have four N-glycosylation sites. Human CD4 molecules can be folded correctly and expressed on the cell surfaces, as well as get infected by HIV virus only when these sites are all glycosylated [13,14,15]. (2) In the TCRαβ-CD3 complex, CD3δ chain has one high mannose N-glycan and one complex N-glycan, while in TCRγδ-CD3 complex, CD3δ chain has two complex N-glycan.…”

Section: Effects Of N-glycans On the T Cells Functions/cellular Immunitymentioning

confidence: 99%

Roles of Glycans and Glycopeptides in Immune System and Immune-Related Diseases

Zhang

2006

CMC

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Almost all of the key molecules in organisms involved in the innate and adaptive immune response (including immunoglobulins, cytokines and cytokine receptors, complements, CD molecules, adhesions, T-cell receptors and major histocompatibility complex molecules) are glycoproteins. Besides, foreign antigens, such as many viral envelope proteins, are glycoproteins too. Carbohydrates attached to proteins or peptides are classified by the nature of their linkages to the protein, mostly as either N-linked (N-acetylglucosamine to asparagines) or O-linked (N-acetylgalactosamine to serine or threonine) oligosaccharides. The glycans have three major roles: firstly, the sugars confer stability on the proteins to which they are attached, protecting them from proteases and non-specific protein-protein interactions. Secondly, glycans play key roles in signal transduction, control of cell development and differentiation. Thirdly, specific regions of the oligosaccharide chains provide recognition epitopes, which influence innate and adaptive immune responses. Glycopeptides not only provide specific oligosaccharides, but also have specific information of amino acids sequences. The glycans and glycopeptides not only influence the structure and functions of immune molecules, but also influence the immune response. In addition, changes in glycans or glycopeptides may have a significant role in a variety of human immune-related diseases, such as rheumatoid, autoimmune disease, Wiskott-Aldrich syndrome, infection disease, cancer, etc. In this article, the roles of N-, O-glycans and glycopeptides in immune system and immune-related diseases are discussed. The potential therapeutic significance of the information is also mentioned.

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“…N -pentafluorobenzyl-1-DNJ was synthesized, and it was found that it inhibited the secretion of interleukin-4 and the expression of CD4. This molecule may be a new immunosuppressant candidate for treating Th2-mediated immune diseases [14]. In other literature, N -Alkyl-DNJ also inhibits α-glucosidase, and the position of the alkyl chain (α-1-C, β-1-C, or N -alkyl derivatives) greatly influences the selectivity and potency [15].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Activity Evaluation of Novel N-benzyl Deoxynojirimycin Derivatives for Use as α-Glucosidase Inhibitors

et al. 2019

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To obtain α-glucosidase inhibitors with high activity, 19 NB-DNJDs (N-benzyl-deoxynojirimycin derivatives) were designed and synthesized. The results indicated that the 19 NB-DNJDs displayed different inhibitory activities towards α-glucosidase in vitro. Compound 18a (1-(4-hydroxy-3-methoxybenzyl)-2-(hydroxymethyl) piperidine-3,4,5-triol) showed the highest activity, with an IC50 value of 0.207 ± 0.11 mM, followed by 18b (1-(3-bromo-4-hydroxy-5-methoxybenzyl)-2-(hydroxymethyl) piperidine-3,4,5-triol, IC50: 0.276 ± 0.13 mM). Both IC50 values of 18a and 18b were significantly lower than that of acarbose (IC50: 0.353 ± 0.09 mM). According to the structure-activity analysis, substitution of the benzyl and bromine groups on the benzene ring decreased the inhibition activity, while methoxy and hydroxyl group substitution increased the activity, especially with the hydroxyl group substitution. Molecular docking results showed that three hydrogen bonds were formed between compound 18a and amino acids in the active site of α-glucosidase. Additionally, an arene‒arene interaction was also modelled between the phenyl ring of compound 18a and Arg 315. The three hydrogen bonds and the arene‒arene interaction resulted in a low binding energy (–5.8 kcal/mol) and gave 18a a higher inhibition activity. Consequently, compound 18a is a promising candidate as a new α-glucosidase inhibitor for the treatment of type Ⅱ diabetes.

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Specific inhibition effects of N -pentafluorobenzyl-1-deoxynojirimycin on human CD4+ T cells

Cited by 10 publications

References 11 publications

Iminosugars as Immunomodulating Agents: Synthesis and Biological Activities of 1‐Deoxynojirimycin and Related Compounds

Iminosugars as Immunomodulating Agents: Synthesis and Biological Activities of 1‐Deoxynojirimycin and Related Compounds

Roles of Glycans and Glycopeptides in Immune System and Immune-Related Diseases

Design, Synthesis, and Activity Evaluation of Novel N-benzyl Deoxynojirimycin Derivatives for Use as α-Glucosidase Inhibitors

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