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

MedChemComm, ISSN: 2040-2511, Vol: 7, Issue: 2, Page: 365-370
2016
  • 5
    Citations
  • 0
    Usage
  • 13
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    5
    • Citation Indexes
      5
  • Captures
    13

Article Description

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.

Bibliographic Details

Jiajia Wang; Xiaomin Wang; Yunyan Zhao; Xiaoyao Ma; Yue Wan; Zhongwei Chen; Hao Chen; Jing Li; Peng George Wang; Wei Zhao; Lei Li; Hao Gan

Royal Society of Chemistry (RSC)

Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics; Chemistry

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