(1) Background. Inflammation is reported to be a key factor in neurodegeneration. The microglia are immune cells present in the central nervous system; their activation results in the release of inflammatory cytokines and is thought to be related to aging and neurodegenerative disorders, such as Alzheimer's disease. (2) Methods. A mouse BV-2 microglia cell line was activated using LPS and the anti-inflammatory cucumber-derived iminosugar amino acid idoBR1, (2,3,4,5)-3,4,5-trihydroxypiperidine-2-carboxylic acid, was used alongside dexamethasone as the control to determine whether it could reduce the inflammatory responses. (3) Results. A dose-dependent reduction in the LPS-induced production of the proinflammatory factors TNFα, IL-6, and nitric oxide and the transcription factor NF-B was found. (4) Conclusions. Further investigations of the anti-inflammatory effects of idoBR1 in other models of neurodegenerative diseases are warranted.
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http://dx.doi.org/10.3390/molecules27103342 | DOI Listing |
JACS Au
March 2024
Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Nankang, Taipei 115201, Taiwan.
The use of pharmacological chaperones (PCs) to stabilize specific enzymes and impart a therapeutic benefit is an emerging strategy in drug discovery. However, designing molecules that can bind optimally to their targets at physiological pH remains a major challenge. Our previous study found that dibasic polyhydroxylated pyrrolidine exhibited superior pH-selective inhibitory activity and chaperoning activity for human α-galactosidase A (α-Gal A) compared with its monobasic parent molecule, .
View Article and Find Full Text PDFChemistry
February 2024
Unité Mixte de Recherche (UMR) INRS-UQAC, Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique (INRS), Chicoutimi & Laval, Québec, G7H 2B1, Canada.
In this work, we present a metal-free coupling protocol for the regio- and stereoselective C3-thioarylation of 6-amino-2,3,6-trideoxy-d-manno-oct-2-ulosonic acid (iminoKdo). The developed procedure enables the coupling of electron-rich, electron-deficient, and hindered arylthiols, providing a series of C3-modified iminoKdo derivatives in moderate to good yields. Elucidation of active species through controlled experimental studies and time-lapse P NMR analysis provides insights into the reaction mechanism.
View Article and Find Full Text PDFBeilstein J Org Chem
March 2023
Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 845 38 Bratislava, Slovakia.
A synthesis of 1,4-imino-ᴅ-lyxitols and their -arylalkyl derivatives altered at C-5 is reported. Their inhibitory activity and selectivity toward four GH38 α-mannosidases (two Golgi types: GMIIb from and AMAN-2 from , and two lysosomal types: LManII from and JBMan from ) were investigated. 6-Deoxy-DIM was found to be the most potent inhibitor of AMAN-2 ( = 0.
View Article and Find Full Text PDFPlant Physiol
May 2023
State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400715, China.
As the prevalence of diabetes continues to increase, the number of individuals living with diabetes complications will reach an unprecedented magnitude. Continuous use of some synthetic agents to reduce blood glucose levels causes severe side effects, and thus, the demand for nontoxic, affordable drugs persists. Naturally occurring compounds, such as iminosugars derived from the mulberry (Morus spp.
View Article and Find Full Text PDFOrg Biomol Chem
August 2022
Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany.
Strategies for synthesizing polyhydroxylated piperidines such as iminosugars have received broad attention. These substances are known to interact with carbohydrate related enzymes, glycosidases and glycosyltransferases, to which also the large enzyme families of chitin synthases and cellulose synthases belong. Many chemical and biological aspects of chitin synthases remain unexplored due to the fact that modulating substances are hardly available or expensive.
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