Substituted 4-oxo-crotonic acid derivatives as a new class of protein kinase B (PknB) inhibitors: synthesis and SAR study. Issue 8 (17th January 2017)

• Record Type: Journal Article
• Authors: Xu, Changliang; Bai, Xiaoguang; Xu, Jian; Ren, Jinfeng; Xing, Yun; Li, Ziqiang; Wang, Juxian; Shi, Jingjing; Yu, Liyan; Wang, Yucheng
• Is Part Of: RSC advances. Volume 7:Issue 8(2017)
• Page Start: 4763
• Page End: 4775
• Publication Date: 2017-01-17
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c6ra24953a
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Structure–activity relationship (SAR) study of a series of unsaturated crotonic acid derivatives as potential PknB inhibitors. Abstract : Protein kinase B (PknB) is an essential serine/threonine protein kinase required for Mycobacterium tuberculosis ( M. tb ) cell division and cell-wall biosynthesis. A high throughput screen using PknB identified a ( E )-4-oxo-crotonic acid inhibitor, named YH-8, which was used as a scaffold for SAR investigations. A significant improvement in enzyme affinity was achieved. The results indicated that the α, β-unsaturated ketone scaffold and " trans -" configuration are essential for the activity against PknB. And compounds with an aryl group, especially with electron-withdrawing substituents on benzene ring, exhibited four fold potency than that ofYH-8 .