Iminosugars as glycosyltransferase inhibitors: synthesis of polyhydroxypyrrolidines and their evaluation on chitin synthase activity
| Autor: | Isabelle Gautier-Lefebvre, Georges Guillerm, Murielle Muzard, Jean-Bernard Behr |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Antifungal Agents
Glycosylation Molecular Conformation Microbial Sensitivity Tests macromolecular substances Cell wall Structure-Activity Relationship chemistry.chemical_compound Biosynthesis Chitin Drug Discovery Glycosyltransferase Structure–activity relationship Chitin Synthase Pharmacology chemistry.chemical_classification Chitin synthase activity biology fungi Organic Chemistry Fungi Structural component Stereoisomerism General Medicine Chitin synthase Pyrrolidinones Imino Sugars carbohydrates (lipids) Enzyme chemistry Biochemistry biology.protein |
| Zdroj: | European Journal of Medicinal Chemistry. 40:1255-1261 |
| ISSN: | 0223-5234 |
| Popis: | Chitin synthase is an enzyme involved in the biosynthesis of chitin, a major structural component of the cell wall of many fungi. Since chitin is absent in vertebrates, chitin synthase has been envisaged as a valuable target in the search for new antifungal agents. In this report, a series of C-2 substituted polyhydroxypyrrolidines were designed and synthesized with the aim of mimicking the glycosylcation involved at the transition state of the enzymatic reaction governed by chitin synthase. Some of these models displayed chitin synthase inhibition in the millimolar range. However, no significant antifungal activity was noted on a panel of fungal strains. |
| Databáze: | OpenAIRE |
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