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.

Structure-based virtual screening to get new scaffold inhibitors of the Ser/Thr protein kinase PknB from Mycobacterium tuberculosis / Coluccia, Antonio; LA REGINA, Giuseppe; Barilone, Nathalie; Lisa, María Natalia; Brancale, Andrea; André Leroux, Gwenaëlle; Alzari, Pedro M.; Silvestri, Romano. - In: LETTERS IN DRUG DESIGN & DISCOVERY. - ISSN 1570-1808. - STAMPA. - 13:(2016), pp. 1012-1018. [10.2174/1570180813666160801162204]

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

COLUCCIA, Antonio;LA REGINA, GIUSEPPE;SILVESTRI, Romano
2016

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.
2016
ser; Thr protein kinase PknB; mycobacterium tuberculosis; virtual screening; indole
01 Pubblicazione su rivista::01a Articolo in rivista
Structure-based virtual screening to get new scaffold inhibitors of the Ser/Thr protein kinase PknB from Mycobacterium tuberculosis / Coluccia, Antonio; LA REGINA, Giuseppe; Barilone, Nathalie; Lisa, María Natalia; Brancale, Andrea; André Leroux, Gwenaëlle; Alzari, Pedro M.; Silvestri, Romano. - In: LETTERS IN DRUG DESIGN & DISCOVERY. - ISSN 1570-1808. - STAMPA. - 13:(2016), pp. 1012-1018. [10.2174/1570180813666160801162204]
File allegati a questo prodotto
File Dimensione Formato  
Coluccia_Structure-based_2016.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 480.44 kB
Formato Adobe PDF
480.44 kB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/907866
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 4
social impact