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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