Poláková, M., Stanton, R., Wilson, I.B., Holková, I., Šesták, S., Machová, E., Jandová, Z., Kóňa, J. (2015). 'Click chemistry' synthesis of 1-(α-d-mannopyranosyl)-1,2,3-triazoles for inhibition of α-mannosidases.  Carbohydr. Res. 406(): 34--40.

FBrf0227645

Research paper

Three new triazole conjugates derived from d-mannose were synthesized and assayed in in vitro assays to investigate their ability to inhibit α-mannosidase enzymes from the glycoside hydrolase (GH) families 38 and 47. The triazole conjugates were more selective for a GH47 α-mannosidase (Aspergillus saitoi α1,2-mannosidase), showing inhibition at the micromolar level (IC50 values of 50-250 μM), and less potent towards GH38 mannosidases (IC50 values in the range of 0.5-6 mM towards jack bean α-mannosidase or Drosophila melanogaster lysosomal and Golgi α-mannosidases). The highest selectivity ratio [IC50(GH38)/IC50(GH47)] of 100 was exhibited by the phenyltriazole conjugate. To understand structure-activity properties of synthesized compounds, 3-D complexes of inhibitors with α-mannosidases were built using molecular docking calculations.

PMC4382718 (PMC) (EuropePMC)