Discovery of a potent angiotensin converting enzyme inhibitor via virtual screening. Issue 16 (15th August 2017)

• Record Type: Journal Article
• Authors: Ke, Zhipeng; Su, Zhenzhen; Zhang, Xinzhuang; Cao, Zeyu; Ding, Yue; Cao, Liang; Ding, Gang; Wang, Zhenzhong; Liu, Haichun; Xiao, Wei
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 16(2017)
• Page Start: 3688
• Page End: 3692
• Publication Date: 2017-08-15
• Subjects: Angiotensin converting enzyme -- ACE -- Drug discovery -- Virtual screening -- In silico; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.07.016
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Virtual screening method was utilized to search a natural compounds database to obtain ACE inhibitors. 36 natural compounds from hits were tested the inhibitory activity of ACE kinase. To discover three leads against ACE, such as Licochalcone A, Echinatin and EGCG. Structure-activity relationship was analysis in order to give some clues for the further research. Abstract: Prompted by the prominent role of angiotensin converting enzyme (ACE) in hypertension, heart failures, myocardial infarction and diabetic nephropathy, we have attempted to discover novel ACE inhibitors through ligand-based virtual screening. Molecular docking method and rigorously validated model was utilized to search a natural compounds database. Finally, 36 compounds were randomly selected and subjected to in vitro ACE kinase inhibitory assay using fluorescence assays method. The results showed that three compounds (Licochalcone A, Echinatin and EGCG) have strong potential to be developed as a new class of ACE inhibitors. Further chemical modification via fragment modifications guided by structure and ligand-based computational methodologies can lead to discover better agents as potential clinical candidates.