Use of structure-based virtual screening in the investigation of novel human sialidase inhibitors

Recent studies have determined the molecular mechanisms underlying the pathological alterations of sialic acid or its conjugates in various human disease states, and the sialic acid modifying enzyme sialidase has been adopted as an attractive therapeutic option for diseases like cancer, diabetes, inflammation, and arteriosclerosis. Isoform human sialidase inhibitors are also a good chemical tool for exploring the differential functions of human sialidases. In the current study, structure-based virtual screening was attempted to identify the compounds containing novel structures for human sialidase inhibition. The best-hit compound, containing a furan core structure with a dicarboxylic acid group, was purchased from Maybridge Chemical Company and was evaluated for its inhibitory activity against all four types of sialidases. This is the first report on the structure-based virtual screening of human sialidases and provides some structural insights for further efforts in this area.