Broad spectrum antiprotozoal agents that inhibit histone deacetylase: structure-activity relationships of apicidin. Part 2

  • Bioorg Med Chem Lett. 2001 Jan 22;11(2):113-7. doi: 10.1016/s0960-894x(00)00605-3.
S L Colletti  1 ,  R W Myers ,  S J Darkin-Rattray ,  A M Gurnett ,  P M Dulski ,  S Galuska ,  J J Allocco ,  M B Ayer ,  C Li ,  J Lim ,  T M Crumley ,  C Cannova ,  D M Schmatz ,  M J Wyvratt ,  M H Fisher ,  P T Meinke
Affiliations
  • 1. Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ 07065, USA. [email protected]
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.