Discovery of a Selective Series of Inhibitors of Plasmodium falciparum HDACs

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• 作者：Jesus M. Ontoria ; Giacomo Paonessa ; Simona Ponzi ; Federica Ferrigno ; Emanuela Nizi ; Ilaria Biancofiore ; Savina Malancona ; Rita Graziani ; David Roberts ; Paul Willis ; Alberto Bresciani ; Nadia Gennari ; Ottavia Cecchetti ; Edith Monteagudo ; Maria V. Orsale ; Maria Veneziano ; Annalise Di Marco ; Antonella Cellucci ; Ralph Laufer ; Sergio Altamura ; Vincenzo Summa ; Steven Harper
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：May 12, 2016
• 年：2016
• 卷：7
• 期：5
• 页码：454-459
• 全文大小：361K
• 年卷期：0
• ISSN：1948-5875

文摘

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.