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

ABSTRACT: 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.

SUBMITTER: Patel V

PROVIDER: S-EPMC2669731 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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

Patel Vishal V Mazitschek Ralph R Coleman Bradley B Nguyen Cokey C Urgaonkar Sameer S Cortese Joseph J Barker Robert H RH Greenberg Edward E Tang Weiping W Bradner James E JE Schreiber Stuart L SL Duraisingh Manoj T MT Wirth Dyann F DF Clardy Jon J

Journal of medicinal chemistry 20090401 8

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 es ...[more]

PMID: 19317450

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