Fragment‐Based Design of Novel Quinazolinon Derivatives as Human Acrosin Inhibitors. (28th March 2013)

• Record Type: Journal Article
• Authors: Ning, Weiwei; Zhu, Ju; Zheng, Canhui; Liu, Xuefei; Song, Yunlong; Zhou, Youjun; Zhang, Xiaomeng; Zhang, Ling; Sheng, Chunquan; Lv, Jiaguo
• Is Part Of: Chemical biology & drug design. Volume 81:Number 4(2013:Apr.)
• Page Start: 437
• Page End: 441
• Publication Date: 2013-03-28
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12106
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" xml:lang="en" id="cbdd12106-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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. <italic>In vitro</italic> anti‐acrosin assay revealed that all the compounds showed potent human acrosin inhibitory activities. In particular, compounds <bold>5c</bold> and <bold>5g</bold> 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.</p> </abstract>