Gluco-1 H-imidazole: A New Class of Azole-Type β-Glucosidase Inhibitor

Sybrin P Schröder, Liang Wu, Marta Artola, Thomas Hansen, Wendy A Offen, Maria J. Ferraz, Kah-Yee Li, Johannes M F G Aerts, Gijsbert A. Van Der Marel, Jeroen D C Codée, Gideon J Davies, Herman S. Overkleeft

Research output: Contribution to journalArticlepeer-review


Gluco-azoles competitively inhibit glucosidases by transition-state mimicry and their ability to interact with catalytic acid residues in glucosidase active sites. We noted that no azole-type inhibitors described, to date, possess a protic nitrogen characteristic for 1 H-imidazoles. Here, we present gluco-1 H-imidazole, a gluco-azole bearing a 1 H-imidazole fused to a glucopyranose-configured cyclitol core, and three close analogues as new glucosidase inhibitors. All compounds inhibit human retaining β-glucosidase, GBA1, with the most potent ones inhibiting this enzyme (deficient in Gaucher disease) on a par with glucoimidazole. None inhibit glucosylceramide synthase, cytosolic β-glucosidase GBA2 or α-glucosidase GAA. Structural, physical and computational studies provide first insights into the binding mode of this conceptually new class of retaining β-glucosidase inhibitors.

Original languageEnglish
Pages (from-to)1-4
Number of pages4
JournalJournal of the American Chemical Society
Early online date30 Mar 2018
Publication statusPublished - 2018

Bibliographical note

© 2018 American Chemical Society. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.


  • Journal Article

Cite this