Issue 2, 2016

Synthesis and biological evaluation of d-gluconhydroximo-1,5-lactam and its oxime-substituted derivatives as pharmacological chaperones for the treatment of Gaucher disease

Abstract

D-Gluconhydroximo-1,5-lactam and its oxime-substituted derivatives were prepared and assessed for inhibition and pharmacological chaperone (PC) activities in Gaucher disease cell lines derived from N370S. The most active compound, O-(D-glucopyranosylidene) amino-Z-N-dodecylcarbamate (38), gave a nearly 2.0-fold increase in N370S β-GCase activity at 12.5 μM with no inhibition to other commercially available glucosidases. Docking studies of ligand–enzyme interactions have also been conducted to account for the results of enzyme activity increase. All these results demonstrate that compound 38 is a promising PC for the treatment of GD.

Graphical abstract: Synthesis and biological evaluation of d-gluconhydroximo-1,5-lactam and its oxime-substituted derivatives as pharmacological chaperones for the treatment of Gaucher disease

Supplementary files

Article information

Article type
Research Article
Submitted
02 Nov 2015
Accepted
12 Dec 2015
First published
15 Dec 2015

Med. Chem. Commun., 2016,7, 365-370

Synthesis and biological evaluation of D-gluconhydroximo-1,5-lactam and its oxime-substituted derivatives as pharmacological chaperones for the treatment of Gaucher disease

J. Wang, X. Wang, Y. Zhao, X. Ma, Y. Wan, Z. Chen, H. Chen, H. Gan, J. Li, L. Li, P. G. Wang and W. Zhao, Med. Chem. Commun., 2016, 7, 365 DOI: 10.1039/C5MD00501A

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