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.
Vishal Patel  1 ,  Ralph Mazitschek ,  Bradley Coleman ,  Cokey Nguyen ,  Sameer Urgaonkar ,  Joseph Cortese ,  Robert H Barker ,  Edward Greenberg ,  Weiping Tang ,  James E Bradner ,  Stuart L Schreiber ,  Manoj T Duraisingh ,  Dyann F Wirth ,  Jon Clardy
Affiliations
  • 1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
PMID: 19317450 DOI: 10.1021/jm801654y
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.