Design, synthesis, and biological evaluation of human sialidase inhibitors. Part 1: Selective inhibitors of lysosomal sialidase (NEU1)

We here report the design and synthesis of selective human lysosomal sialidase (NEU1) inhibitors. A series of amide-linked C9 modified DANA (2-deoxy-2,3-dehydro-N-acetylneuraminic acid) analogues were synthesized and their inhibitory activities against all four human sialidases (NEU1–NEU4) were determined. Structure-based approach was used to investigate the basis of selectivity of the compounds with experimentally observed activity. Results from the present study are found to be informative in a qualitative manner for the further design of isoform selective human sialidase inhibitors for therapeutic value.

Graphical abstractThe synthesis and human sialidase inhibitory activities of some amide-linked C9 modified DANA analogues 10a–j are described.Figure optionsDownload full-size imageDownload as PowerPoint slide