化学
药效团
结核分枝杆菌
脚手架
虚拟筛选
激酶
支架蛋白
蛋白激酶A
IC50型
计算生物学
生物化学
生物
肺结核
医学
信号转导
体外
病理
生物医学工程
作者
Antonio Coluccia,Giuseppe La Regina,Nathalie Barilone,María‐Natalia Lisa,Andrea Brancale,Gwénaëlle André-Leroux,Pedro M. Alzari,Romano Silvestri
出处
期刊:Letters in Drug Design & Discovery
[Bentham Science]
日期:2016-10-31
卷期号:13 (10): 1012-1018
被引量:4
标识
DOI:10.2174/1570180813666160801162204
摘要
In search of new inhibitors of the Ser/Thr protein kinase PknB from Mycobacterium tuberculosis we carried out a structure-based virtual screening study to identify ATP-competitive inhibitors of this enzyme. These studies point out that N-phenylmethylindole-2-carboxamide is a promising scaffold for the development of new PknB inhibitors. We synthesized a small set of analogue compounds to assess the pharmacophore structural requirements and to optimize the inhibitory activity against PknB. This strategy led to the identification of compound 3, endowed with an IC50 of 20 μM, which provides a novel scaffold for further improvement of PknB inhibitors. Keywords: Ser, Thr protein kinase PknB, mycobacterium tuberculosis, virtual screening, indole.
科研通智能强力驱动
Strongly Powered by AbleSci AI