Potent GH20 N-Acetyl-β-d-hexosaminidase Inhibitors: N-Substituted 3-acetamido-4-amino-5-hydroxymethyl-cyclopentanediols

Patrick Weber; Seyed A Nasseri; Bettina M Pabst; Ana Torvisco; Philipp Müller; Eduard Paschke; Marion Tschernutter; Werner Windischhofer; Stephen G Withers; Tanja M Wrodnigg; Arnold E Stütz

doi:10.3390/molecules23030708

Potent GH20 N-Acetyl-β-d-hexosaminidase Inhibitors: N-Substituted 3-acetamido-4-amino-5-hydroxymethyl-cyclopentanediols

Molecules. 2018 Mar 20;23(3):708. doi: 10.3390/molecules23030708.

Authors

Affiliations

¹ Glycogroup, Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria. patrick.weber@tugraz.at.
² Chemistry Department, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada. snasseri@chem.ubc.ca.
³ Laboratory of Metabolic Diseases, Department of Pediatrics, MedUni Graz, Auenbruggerplatz 30, A-8036 Graz, Austria. bettina.pabst@medunigraz.at.
⁴ Institute of Inorganic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria. ana.torviscogomez@tugraz.at.
⁵ Institute of Inorganic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria. philipp.mueller@tugraz.at.
⁶ Laboratory of Metabolic Diseases, Department of Pediatrics, MedUni Graz, Auenbruggerplatz 30, A-8036 Graz, Austria. eduard.paschke@inode.at.
⁷ Laboratory of Metabolic Diseases, Department of Pediatrics, MedUni Graz, Auenbruggerplatz 30, A-8036 Graz, Austria. marion.tschernutter@medunigraz.at.
⁸ Laboratory of Metabolic Diseases, Department of Pediatrics, MedUni Graz, Auenbruggerplatz 30, A-8036 Graz, Austria. werner.windischhofer@medunigraz.at.
⁹ Chemistry Department, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada. withers@chem.ubc.ca.
¹⁰ Glycogroup, Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria. t.wrodnigg@tugraz.at.
¹¹ Glycogroup, Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria. stuetz@tugraz.at.

Abstract

From 1,2;3,4-di-O-isopropylidene-d-galactopyranose, a preliminary series of highly functionalized amino(hydroxymethyl)cyclopentanes was easily available. These amine-containing basic carbasugars featuring the d-galacto configuration are potent inhibitors of the GH20 β-d-hexosaminidases probed and may bear potential as regulators of N-acetyl-d-hexosaminidase activities in vivo.

Keywords: ">d-hexosaminidase inhibitor; N-acetyl-; Tay-Sachs; aminocyclopentane.

MeSH terms

Crystallography, X-Ray
Cyclopentanes / chemical synthesis
Cyclopentanes / chemistry
Cyclopentanes / pharmacology*
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Molecular Conformation
beta-N-Acetylhexosaminidases / antagonists & inhibitors*
beta-N-Acetylhexosaminidases / metabolism

Substances

Cyclopentanes
Enzyme Inhibitors
beta-N-Acetylhexosaminidases