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Discovery of a Selective Series of Inhibitors of Plasmodium falciparum HDACs.

ABSTRACT: The identification of a new series of P. falciparum growth inhibitors is described. Starting from a series of known human class I HDAC inhibitors a SAR exploration based on growth inhibitory activity in parasite and human cells-based assays led to the identification of compounds with submicromolar inhibition of P. falciparum growth (EC50 < 500 nM) and good selectivity over the activity of human HDAC in cells (up to >50-fold). Inhibition of parasital HDACs as the mechanism of action of this new class of selective growth inhibitors is supported by hyperacetylation studies.

SUBMITTER: Ontoria JM

PROVIDER: S-EPMC4867480 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Discovery of a Selective Series of Inhibitors of Plasmodium falciparum HDACs.

Ontoria Jesus M JM Paonessa Giacomo G Ponzi Simona S Ferrigno Federica F Nizi Emanuela E Biancofiore Ilaria I Malancona Savina S Graziani Rita R Roberts David D Willis Paul P Bresciani Alberto A Gennari Nadia N Cecchetti Ottavia O Monteagudo Edith E Orsale Maria V MV Veneziano Maria M Di Marco Annalise A Cellucci Antonella A Laufer Ralph R Altamura Sergio S Summa Vincenzo V Harper Steven S

ACS medicinal chemistry letters 20160305 5

The identification of a new series of P. falciparum growth inhibitors is described. Starting from a series of known human class I HDAC inhibitors a SAR exploration based on growth inhibitory activity in parasite and human cells-based assays led to the identification of compounds with submicromolar inhibition of P. falciparum growth (EC50 < 500 nM) and good selectivity over the activity of human HDAC in cells (up to >50-fold). Inhibition of parasital HDACs as the mechanism of action of this new c ...[more]

PMID: 27190592

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