Sugar-Derived Amidines and Congeners: Structures, Glycosidase Inhibition and Applications

Glycosidases, the enzymes responsible for the breakdown of glycoconjugates, including di-, oligo-and polysaccharides, are present across all kingdoms of life. The ex-treme chemical stability of the glycosidic bond combined with the catalytic rates achieved by glycosidases makes them among the most proficient of all enzymes. Given their mul-titude of roles in vivo, inhibition of these enzymes is highly attractive with potential in the treatment of a vast array of pathologies ranging from lysosomal storage and diabetes to viral infections. Therefore great efforts have been invested in the last three decades to de-sign and synthesize inhibitors of glycosidases leading to a number of drugs currently on the market. Amongst the vast array of structures that have been disclosed, sugars incorpo-rating an amidine moiety have been the focus of many research groups around the world because of their glycosidase transition state-like structure. In this review, we report and discuss the structure, the inhibition profile, and the use of these molecules, including re-lated structural congeners as transition state analogs.