دورية أكاديمية
Novel glucopyranoside C2-derived 1,2,3-triazoles displaying selective inhibition of O-GlcNAcase (OGA).
العنوان: | Novel glucopyranoside C2-derived 1,2,3-triazoles displaying selective inhibition of O-GlcNAcase (OGA). |
---|---|
المؤلفون: | Igual MO; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Monte Alegre, 14040-930, Ribeirão Preto, Brazil., Nunes PSG; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Monte Alegre, 14040-930, Ribeirão Preto, Brazil., da Costa RM; Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, 14049-900, Ribeirão Preto, Brazil., Mantoani SP; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Monte Alegre, 14040-930, Ribeirão Preto, Brazil., Tostes RC; Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, 14049-900, Ribeirão Preto, Brazil., Carvalho I; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Monte Alegre, 14040-930, Ribeirão Preto, Brazil. Electronic address: ivone.carvalho@pq.cnpq.br. |
المصدر: | Carbohydrate research [Carbohydr Res] 2019 Jan 01; Vol. 471, pp. 43-55. Date of Electronic Publication: 2018 Oct 26. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0043535 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-426X (Electronic) Linking ISSN: 00086215 NLM ISO Abbreviation: Carbohydr Res Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: Amsterdam. |
مواضيع طبية MeSH: | Enzyme Inhibitors/*chemical synthesis , Triazoles/*chemical synthesis , beta-N-Acetylhexosaminidases/*antagonists & inhibitors, Animals ; Cell Survival/drug effects ; Cells, Cultured ; Cycloaddition Reaction ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Muscle, Smooth, Vascular/cytology ; Muscle, Smooth, Vascular/drug effects ; Myocytes, Smooth Muscle/cytology ; Myocytes, Smooth Muscle/drug effects ; Rats ; Structure-Activity Relationship ; Triazoles/chemistry ; Triazoles/pharmacology |
مستخلص: | O-GlcNAcylation or O-GlcNAc modification is a post-translational modification of several proteins responsible for fundamental cellular processes. Dysregulation of the O-GlcNAc pathway has been linked to the etiology of several diseases such as neurodegenerative and cardiovascular diseases, type 2 diabetes and cancer. O-GlcNAcase (OGA) catalyzes the removal of O-GlcNAc from the modified proteins and several carbohydrate-based OGA inhibitors have been synthesized to understand the role of O-GlcNAc-modified proteins in physiological and pathological conditions. However, many of the inhibitors lack selectivity for OGA over lysosomal hexosaminidases A and B. Aiming the selectively inhibition of OGA, we propose herein the synthesis of twelve novel glucopyranoside derivatives exploring the bioisosteric replacement of the GlcNAc 2-acetamide group by 1,4-disubstituted 1,2,3-triazole ring, bearing a variety of central chains with different shapes. Compounds were readily prepared through "Copper(I) Catalyzed Azide/Alkyne Cycloaddition" (CuAAC) reaction between a sugar azide and different terminal alkynes. Initial Western Blot analyses and further inhibitory assays proved that compounds 6a (IC (Copyright © 2018 Elsevier Ltd. All rights reserved.) |
فهرسة مساهمة: | Keywords: 1,2,3-Triazole; Click chemistry; O-GlcNAcase; O-GlcNAcylation; Selective inhibitors |
المشرفين على المادة: | 0 (Enzyme Inhibitors) 0 (Triazoles) EC 3.2.1.50 (hexosaminidase C) EC 3.2.1.52 (beta-N-Acetylhexosaminidases) |
تواريخ الأحداث: | Date Created: 20181110 Date Completed: 20190415 Latest Revision: 20190415 |
رمز التحديث: | 20221213 |
DOI: | 10.1016/j.carres.2018.10.007 |
PMID: | 30412832 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1873-426X |
---|---|
DOI: | 10.1016/j.carres.2018.10.007 |