Iminosugar-based galactoside mimics as inhibitors of galactocerebrosidase: SAR studies and comparison with other lysosomal galactosidases.

2014: NAsano; ABiela-Banaś; SFront; EGallienne; KIkeda-Obatake; ORMartin; FOulaïdi; DAWenger;

ChemMedChem.2014;9(12):2647-52.10.1002/cmdc.201402411.

NLM PMID: 25377381

Article abstract

Several families of iminosugar-based galactoside mimics were designed, synthesized, and evaluated as galactocerebrosidase (GALC) inhibitors. They were also tested as inhibitors of lysosomal β- and α-galactosidases in order to find new potent and selective pharmacological chaperones for treatment of the lysosomal storage disorder, Krabbe disease. Whereas 1-C-alkyl imino-L-arabinitols are totally inactive toward the three enzymes, 1-C-alkyl imino-D-galactitols were found to be active only toward α-galactosidase A. Finally, 1-N-iminosugars provided the best results, as 4-epi-isofagomine was found to be a good inhibitor of both lysosomal β-galactosidase and GALC. Further elaboration of this structure is required to achieve selectivity between these two galactosidases.

Research Topics
• Diseases
   Leukodystrophy, Globoid Cell

Title and Abstract from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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Last MEDLINE®/PubMed® update: 1st of December 2015