Inhibition of human neuraminidase 3 (NEU3) by C9-triazole derivatives of 2,3-didehydro-N-acetyl-neuraminic acid

We report the synthesis of a series of C9 and N5Ac modified analogs of 2,3-didehydro-N-acetyl-neuraminic acid (DANA) and their inhibitory potency for the human neuraminidase 3 (NEU3) enzyme. We were able to generate a small library of compounds through the synthesis of azide derivatives of DANA, followed by Cu-catalyzed azide–alkyne cycloaddition (CuAAC) to generate triazole-containing inhibitors. Our results suggest that NEU3 can tolerate large hydrophobic groups at the C9 position; however, none of the derivatives made at the N5Ac side-chain were active. We identify three new inhibitors that have comparable potency to the best reported inhibitors of the enzyme.

Graphical abstractSynthetic inhibitors were used to test the tolerance of the NEU3 active site for modifications of DANA; three potent inhibitors were identified.Figure optionsDownload full-size imageDownload as PowerPoint slide