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

By Ontoria, Jesus M.; Paonessa, Giacomo; Ponzi, Simona; Ferrigno, Federica; Nizi, Emanuela; Biancofiore, Ilaria; Malancona, Savina; Graziani, Rita; Roberts, David; Willis, Paul; et al
From ACS Medicinal Chemistry Letters (2016), 7(5), 454-459. Language: English, Database: CAPLUS, DOI:10.1021/acsmedchemlett.5b00468

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 compds. 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.