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Structure-based virtual screening to get news scaffold inhibitors of the Ser/Thr Protein Kinase PknB from Mycobacterium tuberculosis

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Coluccia, Antonio | La Regina, Giuseppe | Barilone, Nathalie | Lisa, Maria Natalia | Brancale, Andrea | André-Leroux, Gwenaëlle | Alzari, Pedro M. | Silvestri, Romano

Edité par CCSD ; Bentham Science Publishers -

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 mu M, which provides a novel scaffold for further improvement of PknB inhibitors.

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