Abstract
Herein, we present an alternative and elegant synthetic approach toward powerful β-glucosidase inhibitor isofagomine. Derivatizations of the ring nitrogen provided a selected set of N-modified isofagomine analogues. Biological evaluation of these compounds showed a remarkable change in potency as well as α/β-preference for various glycosidases from different sources when compared to the parent compound isofagomine. Overall, the conducted N-modification improved the potency against α-glucosidase from Saccharomyces cerevisiae (GH13). Coming along, significant diminished activities toward GH1 family β-glucosidases from three different sources have been observed for all tested derivatives. Moreover, and contrary to isofagomine, deactivations of β-galactosidase from Escherichia coli (GH2) as well as α-mannosidase from Canavalia ensiformis (GH38) have not been verified for this series of compounds.
Original language | English |
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Article number | e202300480 |
Pages (from-to) | 21-34 |
Number of pages | 14 |
Journal | Monatshefte fur Chemie |
Volume | 156 |
Issue number | 1 |
Early online date | 29 May 2024 |
DOIs | |
Publication status | Published - Jan 2025 |
Keywords
- Carbohydrates
- Glycosidase inhibitor
- Glycoside hydrolases
- Henry reaction
- Isofagomine
- N-modification
ASJC Scopus subject areas
- General Chemistry