Premium
Fragment‐Based Design of Novel Quinazolinon Derivatives as Human Acrosin Inhibitors
Author(s) -
Ning Weiwei,
Zhu Ju,
Zheng Canhui,
Liu Xuefei,
Song Yunlong,
Zhou Youjun,
Zhang Xiaomeng,
Zhang Ling,
Sheng Chunquan,
Lv Jiaguo
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12106
Subject(s) - acrosin , fragment (logic) , chemistry , computational biology , stereochemistry , combinatorial chemistry , biochemistry , biology , computer science , genetics , algorithm , semen , acrosome
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.