Structure-based virtual screening to get new scaffold inhibitors of the Ser/Thr protein kinase PknB from mycobacterium tuberculosis

Coluccia, Antonio, Regina, Giuseppe, Barilone, Nathalie, Lisa, María-Natalia, Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419, André-Leroux, Gwenaëlle, Alzari, Pedro and Silvestri, Romano 2016. Structure-based virtual screening to get new scaffold inhibitors of the Ser/Thr protein kinase PknB from mycobacterium tuberculosis. Letters in Drug Design & Discovery 13 (10) , pp. 1012-1018. 10.2174/1570180813666160801162204

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RS Pharmacy and materia medica
Publisher:	PubMed Central
ISSN:	1570-1808
Date of First Compliant Deposit:	2 December 2016
Date of Acceptance:	27 July 2016
Last Modified:	05 Jan 2024 17:41
URI:	https://orca.cardiff.ac.uk/id/eprint/96596

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