An overview of therapeutic potential of N-alkylated 1-deoxynojirimycin congeners.

Polyhydroxylated alkaloids display a wide range of biological activities, suggesting their use in the treatment of various diseases. Their most famous representative, 1-deoxynojirimycin (DNJ), is a natural product that shows α- and β-glucosidase inhibition. This molecule has been since converted into two clinically approved drugs i.e., Zavesca® and Glyset®, targeting type I Gaucher's disease and type II diabetes mellitus, respectively. This review examines the therapeutic potential of important DNJ congeners reported in last decade and presents concise mechanism of glycosidase inhibition. A brief overview of substituents conjugation's impact on DNJ scaffold (including N-alkylated DNJ derivatives, mono-valent, di-valent and multivalent DNJ congeners, N-[5-(adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin (AMP-DNM) look alike DNJ based lipophilic derivatives, AMP-DNM based neoglycoconjugates, DNJ click derivatives with varying carboxylic acids and aromatic moieties, conjugates of DNJ and glucose, and N-bridged DNJ analogues) towards various enzymes such as α/β glucosidase, porcine trehalase, as F508del-CFTR correctors, α-mannosidase, human placental β-glucocerebrosidase, N370S β-GCase, α-amylase and insect trehalase as potent and selective inhibitors have been discussed with potential bioactivities, which can provide inspiration for future studies.