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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 &lt; 500 nM) and good selectivity over the activity of human HDAC in cells (up to &gt;50-fold). Inhibition of parasital HDACs as the mechanism of action of this new class of selective growth inhibitors is supported by hyperacetylation studies.

Discovery of a Selective Series of Inhibitors of Plasmodium falciparum HDACs