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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Acetylation
-
Animals
-
Antimalarials / chemistry*
-
Antimalarials / pharmacology
-
Cell Line, Tumor
-
Histone Deacetylase Inhibitors*
-
Histone Deacetylases / chemistry
-
Humans
-
Kinetics
-
Parasitic Sensitivity Tests
-
Plasmodium falciparum / drug effects
-
Plasmodium falciparum / enzymology*
-
Recombinant Proteins / antagonists & inhibitors
-
Recombinant Proteins / chemistry
-
Small Molecule Libraries*
-
Structure-Activity Relationship
Substances
-
Antimalarials
-
Histone Deacetylase Inhibitors
-
Recombinant Proteins
-
Small Molecule Libraries
-
Histone Deacetylases