Enzymatic synthesis of new C-6-acylated derivatives of NAG-thiazoline and evaluation of their inhibitor activities towards fungal β-N-acetylhexosaminidase

β-N-Acetylhexosaminidases (EC 3.2.1.52) from the CAZy glycoside hydrolase families 20 and 84 are two distinct enzyme groups with similar reactivity and different physiological functions, thus selective inhibition of these enzymes is of crucial importance. Here, we report on the lipase-catalyzed synthesis of a set of novel monomeric and dimeric C-6-acylated derivatives of NAG-thiazoline, which is a typical competitive inhibitor of both these enzyme classes. The prepared compounds were tested as potential inhibitors of a fungal GH20 β-N-acetylhexosaminidase from Talaromyces flavus, however, the results of the inhibition tests were quite ambiguous. The observed inhibition was generally weak with some features of competitive inhibition (increase of KM), but the overall pattern appeared indecisive.

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► Novel C-6-acylated NAG-thiazolines were prepared in lipase-catalyzed reactions.
► Both monomeric and dimeric NAG-thiazoline derivatives were synthesized.
► The compounds were tested as β-N-acetylhexosaminidase inhibitors.
► The observed inhibition pattern suggested ambiguous mixed inhibition.