title: 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.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Patel
authors.forename: Ralph
authors.initials: R
authors.lastname: Mazitschek
authors.forename: Bradley
authors.initials: B
authors.lastname: Coleman
authors.forename: Cokey
authors.initials: C
authors.lastname: Nguyen
authors.forename: Sameer
authors.initials: S
authors.lastname: Urgaonkar
authors.forename: Joseph
authors.initials: J
authors.lastname: Cortese
authors.forename: Robert H
authors.initials: RH
authors.lastname: Barker
authors.forename: Edward
authors.initials: E
authors.lastname: Greenberg
authors.forename: Weiping
authors.initials: W
authors.lastname: Tang
authors.forename: James E
authors.initials: JE
authors.lastname: Bradner
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Schreiber
authors.forename: Manoj T
authors.initials: MT
authors.lastname: Duraisingh
authors.forename: Dyann F
authors.initials: DF
authors.lastname: Wirth
authors.forename: Jon
authors.initials: J
authors.lastname: Clardy