title: 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.
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Jesus M
authors.initials: JM
authors.lastname: Ontoria
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Paonessa
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Ponzi
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Ferrigno
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Nizi
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Biancofiore
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Savina
authors.initials: S
authors.lastname: Malancona
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Graziani
authors.affiliation: Medicines for Malaria Venture, ICC , Route de Pré-Bois 20, P.O. Box 1826, 1215 Geneva, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Roberts
authors.affiliation: Medicines for Malaria Venture, ICC , Route de Pré-Bois 20, P.O. Box 1826, 1215 Geneva, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Willis
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bresciani
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Gennari
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Ottavia
authors.initials: O
authors.lastname: Cecchetti
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Edith
authors.initials: E
authors.lastname: Monteagudo
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Orsale
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Veneziano
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Annalise
authors.initials: A
authors.lastname: Di Marco
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Cellucci
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Ralph
authors.initials: R
authors.lastname: Laufer
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Altamura
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Summa
authors.affiliation: Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
authors.forename: Steven
authors.initials: S
authors.lastname: Harper
keywords: 4-arylimidazoles; Malaria; PfHDAC1; Plasmodium falciparum