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

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

Volume: 13 Issue: 10

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

Affiliation:

Keywords: Ser, Thr protein kinase PknB, mycobacterium tuberculosis, virtual screening, indole.

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.

Cite this article as:

Coluccia Antonio, Regina La Giuseppe, Barilone Nathalie, Lisa María-Natalia, Brancale Andrea, André-Leroux Gwenaëlle, Alzari M. Pedro and Silvestri Romano, Structure-based Virtual Screening to Get New Scaffold Inhibitors of the Ser/Thr Protein Kinase PknB from Mycobacterium tuberculosis, Letters in Drug Design & Discovery 2016; 13 (10) . https://dx.doi.org/10.2174/1570180813666160801162204