title: Broad spectrum antiprotozoal agents that inhibit histone deacetylase: structure-activity relationships of apicidin. Part 2.
abstract: Recently isolated at Merck, apicidin inhibits both mammalian and protozoan histone deacetylases (HDACs). The conversion of apicidin, a nonselective nanomolar inhibitor of HDACs, into a series of picomolar indole-modified and parasite-selective tryptophan-replacement analogues is described within this structure-activity study.
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ 07065, USA. steve_colletti@merck.com
authors.forename: S L
authors.initials: SL
authors.lastname: Colletti
authors.forename: R W
authors.initials: RW
authors.lastname: Myers
authors.forename: S J
authors.initials: SJ
authors.lastname: Darkin-Rattray
authors.forename: A M
authors.initials: AM
authors.lastname: Gurnett
authors.forename: P M
authors.initials: PM
authors.lastname: Dulski
authors.forename: S
authors.initials: S
authors.lastname: Galuska
authors.forename: J J
authors.initials: JJ
authors.lastname: Allocco
authors.forename: M B
authors.initials: MB
authors.lastname: Ayer
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Lim
authors.forename: T M
authors.initials: TM
authors.lastname: Crumley
authors.forename: C
authors.initials: C
authors.lastname: Cannova
authors.forename: D M
authors.initials: DM
authors.lastname: Schmatz
authors.forename: M J
authors.initials: MJ
authors.lastname: Wyvratt
authors.forename: M H
authors.initials: MH
authors.lastname: Fisher
authors.forename: P T
authors.initials: PT
authors.lastname: Meinke
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001685:Biological Factors / Q000494:pharmacology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; 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; D007211:Indoles / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000737:chemistry
chemical_list: D000981:Antiprotozoal Agents; D001685:Biological Factors; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D007211:Indoles; D010456:Peptides, Cyclic; C102351:apicidin; D014364:Tryptophan