AI Article Synopsis
- The study focuses on creating eleven derivatives of 1-deoxynojirimycin (DNJ) that include various functional groups like fluorine and sulfur, using advanced chemical techniques.
- The newly synthesized compounds were tested for their effectiveness in inhibiting glycosidases and correcting a specific cystic fibrosis mutation (F508del-CFTR).
- Some unsaturated iminosugars showed similar potency to the drug Miglustat in correcting the CFTR mutation, while introducing fluorine negatively affected their ability to correct the mutation and inhibit certain enzymes.
Article Abstract
The synthesis of eleven 1-deoxynojirimycin (DNJ) derivatives presenting either a monofluoro, difluoro, thiolated or unsaturated N-alkyl chain of various length is described. Exploiting the unsaturated moiety on the nitrogen, fluorine has been introduced through a HF/SbF5 superacid catalysed hydrofluorination and thiol-ene click chemistry allowed introduction of sulfur. The synthetic derivatives have been tested for their ability to inhibit glycosidases and correct F508del-CFTR. Two of the unsaturated iminosugars exhibited potency similar to Miglustat as F508del-CFTR correctors. The thioalkyl iminosugars as well as the corresponding alkyl iminosugars demonstrated low micromolar α-glucosidases and trehalases inhibition. Introduction of fluorine abolished F508del-CFTR correction and trehalase inhibition.
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| http://dx.doi.org/10.1039/c5ob01526j | DOI Listing |
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