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

Autor:	Ontoria JM; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Paonessa G; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Ponzi S; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Ferrigno F; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Nizi E; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Biancofiore I; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Malancona S; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Graziani R; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Roberts D; Medicines for Malaria Venture, ICC , Route de Pré-Bois 20, P.O. Box 1826, 1215 Geneva, Switzerland., Willis P; Medicines for Malaria Venture, ICC , Route de Pré-Bois 20, P.O. Box 1826, 1215 Geneva, Switzerland., Bresciani A; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Gennari N; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Cecchetti O; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Monteagudo E; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Orsale MV; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Veneziano M; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Di Marco A; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Cellucci A; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Laufer R; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Altamura S; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Summa V; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy., Harper S; Departments of Chemistry and Biology, IRBM Science Park , Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2016 Mar 05; Vol. 7 (5), pp. 454-9. Date of Electronic Publication: 2016 Mar 05 (Print Publication: 2016).
DOI:	10.1021/acsmedchemlett.5b00468
Abstrakt:	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.
Databáze:	MEDLINE
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