title: Fragment-based design of novel quinazolinon derivatives as human acrosin inhibitors.
abstract: Human acrosin is a promising target for the male contraceptives. On the basis of the active site of human acrosin, a series of novel quinazolinon compounds were designed by a fragment docking and growing strategy. In vitro anti-acrosin assay revealed that all the compounds showed potent human acrosin inhibitory activities. In particular, compounds 5c and 5g are more active than the known inhibitors. Molecular docking studies revealed that the quinazolinon inhibitors interacted with human acrosin mainly through hydrogen bonding and hydrophobic interactions. The binding mode was also consistent with the structure-activity relationships. The quinazolinon derivatives in this study can serve as new lead structure for the development of novel male contraceptives.
authors: Weiwei
authors: W
authors: Ning
authors: Ju
authors: J
authors: Zhu
authors: Canhui
authors: C
authors: Zheng
authors: Xuefei
authors: X
authors: Liu
authors: Yunlong
authors: Y
authors: Song
authors: Youjun
authors: Y
authors: Zhou
authors: Xiaomeng
authors: X
authors: Zhang
authors: Ling
authors: L
authors: Zhang
authors: Chunquan
authors: C
authors: Sheng
authors: Jiaguo
authors: J
authors: Lv
mesh_terms: D000176:Acrosin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D052999:Quinazolinones; D015842:Serine Proteinase Inhibitors; D000176:Acrosin