Broad spectrum antiprotozoal agents that inhibit histone deacetylase: structure-activity relationships of apicidin. Part 1.
Apicidin, a natural product recently isolated at Merck, inhibits both mammalian and protozoan histone deacetylases (HDACs). The conversion of apicidin, a nanomolar inhibitor of HDACs, into a series of side-chain analogues that display picomolar enzyme affinity is described within this structure-activity study.
Colletti
S L
SL
Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ 07065, USA. steve_colletti@merck.com
Myers
R W
RW
Darkin-Rattray
S J
SJ
Gurnett
A M
AM
Dulski
P M
PM
Galuska
S
S
Allocco
J J
JJ
Ayer
M B
MB
Li
C
C
Lim
J
J
Crumley
T M
TM
Cannova
C
C
Schmatz
D M
DM
Wyvratt
M J
MJ
Fisher
M H
MH
Meinke
P T
PT
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001685:Biological Factors / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D020650:Combinatorial Chemistry Techniques; D016786:Eimeria tenella / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005670:Fusarium / Q000737:chemistry; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D001685:Biological Factors; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; C102351:apicidin