Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum
Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum
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DOI：
10.1021/jm801654y
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发表时间：
2009-04-23
影响因子：
7.3
通讯作者：
Clardy, Jon
中科院分区：
文献类型：
--
作者：
Patel, Vishal;Mazitschek, Ralph;Clardy, Jon
在高通量恶性疟原虫活力测定中测定了偏向于抑制组蛋白脱乙酰酶的约2000个小分子的文库的抗疟活性。对活性化合物在人骨髓瘤细胞系中诱导组蛋白超乙酰化进行交叉分析，以鉴定对恶性疟原虫的选择性超过对人宿主的选择性的HDAC抑制剂。为了验证中靶选择性，表达并纯化pfHDAC-1，并建立pfHDAC-1活性的生物化学测定。
A library of approximately 2000 small molecules biased toward inhibition of histone deacetylases was assayed for antimalarial activity in a high-throughput P. falciparum viability assay. Active compounds were cross-analyzed for induction of histone hyperacetylation in a human myeloma cell line to identify HDAC inhibitors with selectivity for P. falciparum over the human host. To verify on-target selectivity, pfHDAC-1 was expressed and purified and a biochemical assay for pfHDAC-1 activity was established.