Discovery of novel human acrosin inhibitors by virtual screening

摘要

Human acrosin is an attractive target for the discovery of male contraceptive drugs.For the first time,structure-based drag design was applied to discover structurally divcrse human acrosin inhibitors.A parallel virtual screening strategy in combination with pharmacophore-based and docking-based techniques was used to screen the SPECS database.From 16 compounds selected by virtual screening,a total of 10 compounds were found to be human acrosin inhibitors.Compound 2 was found to be the most potent hit (IC50 =14 μM) and its binding mode was investigated by molecular dynamics simulations.The hit interacted with human acrosin mainly through hydrophobic and hydrogen-bonding interactions,which provided a good starting structure for further optimization studies.