Synthesis of NAG-thiazoline-derived inhibitors for β-N-acetyl-d-hexosaminidases

• Fourteen NAG-thiazoline derivatives have been synthesized for the first time.
• The inhibition activity of β-N-acetyl-d-hexosaminidases was studied.
• The activity data show compounds exhibit selective inhibition for GH84 β-N-acetyl-d-hexosaminidase.

β-N-Acetyl-d-hexosaminidases are responsible for the metabolism of glycoconjugates in diverse physiological processes that are important targets for medicine and pesticide development. Fourteen new NAG-thiazoline derivatives were synthesized by cyclization and click reaction using d-glucosamine hydrochloride as the starting material. All the compounds created were characterized by NMR and HRMS spectra. A preliminary bioassay, using four enzymes from two β-N-acetyl-d-hexosaminidase families, showed that most of the compounds synthesized exhibit selective inhibition of GH84 β-N-acetyl-d-hexosaminidase. Among the compounds tested, compounds 5a (IC50=12.6 μM, hOGA) and 5e (IC50=12.5 μM, OfOGA) proved to be a highly selective and potent inhibitor.

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