1. Broad spectrum antiprotozoal agents that inhibit histone deacetylase: structure-activity relationships of apicidin. Part 2.
- Author
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Colletti SL, Myers RW, Darkin-Rattray SJ, Gurnett AM, Dulski PM, Galuska S, Allocco JJ, Ayer MB, Li C, Lim J, Crumley TM, Cannova C, Schmatz DM, Wyvratt MJ, Fisher MH, and Meinke PT
- Subjects
- Animals, Antiprotozoal Agents pharmacology, Biological Factors pharmacology, Cattle, Cell Division drug effects, Cell Line, Combinatorial Chemistry Techniques, Eimeria tenella drug effects, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors pharmacology, Fusarium chemistry, HeLa Cells, Humans, Indoles chemistry, Microbial Sensitivity Tests, Peptides, Cyclic chemical synthesis, Plasmodium falciparum drug effects, Structure-Activity Relationship, Tryptophan chemistry, Antiprotozoal Agents chemical synthesis, Histone Deacetylase Inhibitors, Peptides, Cyclic pharmacology
- 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.
- Published
- 2001
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