Structure-based Virtual Screening to Get New Scaffold Inhibitors of the Ser/Thr Protein Kinase PknB from Mycobacterium tuberculosis

Author(s): Antonio Coluccia, Giuseppe La Regina, Nathalie Barilone, María-Natalia Lisa, Andrea Brancale, Gwenaëlle André-Leroux, Pedro M. Alzari, Romano Silvestri.

Journal Name: Letters in Drug Design & Discovery

Volume 13 , Issue 10 , 2016

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Abstract:

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.

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Article Details

VOLUME: 13
ISSUE: 10
Year: 2016
Page: [1012 - 1018]
Pages: 7
DOI: 10.2174/1570180813666160801162204
Price: $58

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