A remarkable change in inhibition potency and selectivity of isofagomine by simple N-modification

André Culum, Herwig Prasch, Tobias Dorn, Roland Fischer, Ema Gardić, Franziska Schmutz, Magdalena Steinbrugger, Arnold E. Stütz, Patrick Weber, Tanja M. Wrodnigg, Martin Thonhofer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Article numbere202300480
Pages (from-to)21-34
Number of pages14
JournalMonatshefte fur Chemie
Volume156
Issue number1
Early online date29 May 2024
DOIs
Publication statusPublished - Jan 2025

Keywords

  • Carbohydrates
  • Glycosidase inhibitor
  • Glycoside hydrolases
  • Henry reaction
  • Isofagomine
  • N-modification

ASJC Scopus subject areas

  • General Chemistry

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