Discovery of a Selective Series of Inhibitors of Plasmodium falciparum HDACs

被引：31

作者：

Ontoria, Jesus M. ^{[1
,2
]}

Paonessa, Giacomo ^{[1
,2
]}

Ponzi, Simona ^{[1
,2
]}

Ferrigno, Federica ^{[1
,2
]}

Nizi, Emanuela ^{[1
,2
]}

Biancofiore, Ilaria ^{[1
,2
]}

Malancona, Savina ^{[1
,2
]}

Graziani, Rita ^{[1
,2
]}

Roberts, David ^{[3
]}

Willis, Paul ^{[3
]}

Bresciani, Alberto ^{[1
,2
]}

Gennari, Nadia ^{[1
,2
]}

Cecchetti, Ottavia ^{[1
,2
]}

Monteagudo, Edith ^{[1
,2
]}

Orsale, Maria V. ^{[1
,2
]}

Veneziano, Maria ^{[1
,2
]}

Di Marco, Annalise ^{[1
,2
]}

Cellucci, Antonella ^{[1
,2
]}

Laufer, Ralph ^{[1
,2
,4
]}

Altamura, Sergio ^{[1
,2
]}

Summa, Vincenzo ^{[1
,2
]}

Harper, Steven ^{[1
,2
]}

机构：

[1] IRBM Sci Pk, Dept Chem, Via Pontina Km 30,600, I-00071 Rome, Italy

[2] IRBM Sci Pk, Dept Biol, Via Pontina Km 30,600, I-00071 Rome, Italy

[3] ICC, Med Malaria Venture, Route Prebois 20,POB 1826, CH-1215 Geneva, Switzerland

[4] Teva Pharmaceut Ind Ltd, Discovery & Product Dev, POB 8077, IL-4250843 Netanya, Israel

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2016年 / 7卷 / 05期

关键词：

Malaria; Plasmodium falciparum; PfHDAC1; 4-arylimidazoles; HISTONE DEACETYLASE INHIBITOR; ANTIMALARIAL ACTIVITY; MALARIA; ACETYLATION; TARGET; GENES;

D O I：

10.1021/acsmedchemlett.5b00468

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：454 / 459

页数：6

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