Structure-based approach to the identification of a novel group of selective glucosamine analogue inhibitors of Trypanosoma cruzi glucokinase.

•The strategy of structure-based drug design allowed for the determination of selective T. cruzi glucokinase inhibitors.•Crystal structures of T. cruzi glucokinase and its complexes with novel glucosamine analogues were determined.•The inhibitor CBZ-GlcN is the strongest glucokinase inhibitor known to date.•Inhibitors BENZ-GlcN and CBZ-GlcN are highly effective against T. cruzi amastigotes co-cultured in mammalian cells.