Issue 8, 2017, Issue in Progress

Substituted 4-oxo-crotonic acid derivatives as a new class of protein kinase B (PknB) inhibitors: synthesis and SAR study

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 of YH-8.

Graphical abstract: Substituted 4-oxo-crotonic acid derivatives as a new class of protein kinase B (PknB) inhibitors: synthesis and SAR study

Supplementary files

Article information

Article type
Paper
Submitted
09 Oct 2016
Accepted
28 Nov 2016
First published
17 Jan 2017
This article is Open Access
Creative Commons BY license

RSC Adv., 2017,7, 4763-4775

Substituted 4-oxo-crotonic acid derivatives as a new class of protein kinase B (PknB) inhibitors: synthesis and SAR study

C. Xu, X. Bai, J. Xu, J. Ren, Y. Xing, Z. Li, J. Wang, J. Shi, L. Yu and Y. Wang, RSC Adv., 2017, 7, 4763 DOI: 10.1039/C6RA24953A

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