Identification and characterization of small molecule inhibitors of a class I histone deacetylase from Plasmodium falciparum.
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.
Patel
Vishal
V
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
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