Identification of a novel SPT inhibitor WXP-003 by docking-based virtual screening and investigation of its anti-fungi effect

Serine palmitoyltransferase (SPT) plays the key role on catalysing formation of 3-ketodihydrosphingosine, which is first step de novo biosynthesis sphingolipids. SPT linked to many diseases including fungal infection, making it a potential therapeutic target. Thus, logical docking-based virtual screening method was used screen selective inhibitor against fungi, not human. We myriocin-similarity database identify compounds with good binding and poor homology human model. Preliminary bio-assay led discovery promising WXP-003, displayed inhibitory activity diversity fungi strains MIC ranging from 0.78 12.5 ?g/mL. WXP-003 could significantly reduce sphingolipids content in no effect mouse fibroblast cell line L929. Molecular dynamics simulation depicted that SPT/WXP-003 complex formed favoured interactions. Taken together, provided valuable guide for development novel anti-fungal agents.