Discovery of novel human acrosin inhibitors by virtual screening
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.
Human acrosin Virtual screening Male contraceptives Lead structure
Xuefei Liu Guoqiag Dong Jue Zhang Jingjing Qi Canhui Zheng Youjun Zhou Ju Zhu Chunquan Sheng Jiaguo Lü
School of Pharmacy, Second Military Medical University, 325 Guohe Road,Shanghai 200433,Peoples Republic of China
国际会议
南京
英文
203-213
2012-05-13（万方平台首次上网日期，不代表论文的发表时间）