Synthesis of modified D-mannose core derivatives and their impact on GH38 α-mannosidases

•New D-lyxose and D-mannose derived models with five- and modified six-member core.•Triazole and sulfone derivatives for inhibition of the GH family 38 α-mannosidases.•None of the compounds affected dLMII.•Two compounds inhibited dGMIIb albeit weakly (IC50 at mM level).•Contrary to sulfones, all triazoles worked as jack bean α-mannosidase inhibitors. Nine new compounds having five- and modified six-member carbohydrate core derived from D-lyxose or D-mannose, and non-hydrolysable aglycones (benzylsulfonyl or aryl(alkyl)triazolyl) were synthesised to investigate their ability to inhibit the recombinant Drosophila melanogaster homologs of two human GH38 family enzymes: Golgi mannosidase II (dGMIIb) and lysosomal mannosidase (dLMII). Two compounds were weak selective dGMIIb inhibitors showing IC50 at mM level. Moreover, it was found that another GH38 enzyme, commercial jack bean α-mannosidase, was inhibited by triazole conjugates regardless of the carbohydrate core while the corresponding sulfones were inactive.