Identification and characterization of small molecule inhibitors of a class I histone deacetylase from Plasmodium falciparum.

J. Med. Chem.2009 Apr 23;52(8):2185-7. doi:10.1021/jm801654y

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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.

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Identification and characterization of small molecule inhibitors of a class I histone deacetylase from Plasmodium falciparum.

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