Antitrypanosomal structure-activity-relationship study of synthetic cynaropicrin derivatives

  • Bioorg Med Chem Lett. 2014 Feb 1;24(3):794-8. doi: 10.1016/j.bmcl.2013.12.099.
Toyonobu Usuki  1 ,  Makiko Sato  2 ,  Shihori Hara  2 ,  Yukiko Yoshimoto  2 ,  Ryosuke Kondo  2 ,  Stefanie Zimmermann  3 ,  Marcel Kaiser  4 ,  Reto Brun  4 ,  Matthias Hamburger  5 ,  Michael Adams  5
Affiliations
  • 1. Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan. Electronic address: [email protected].
  • 2. Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan.
  • 3. Division of Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4002 Basel, Switzerland.
  • 4. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4002 Basel, Switzerland.
  • 5. Division of Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
PMID: 24433861 DOI: 10.1016/j.bmcl.2013.12.099
Abstract

Cynaropicrin is a guaianolide sesquiterpene lactone with a 5-7-5 tricyclic skeleton, four exo-olefins, and two hydroxyl groups. Recently, it was found that the compound is a potent in vitro and in vivo inhibitor of the protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis (HAT; sleeping sickness). In this Letter, chemical derivatization of cynaropicrin and the structure-activity-relationship (SAR) study against T. brucei is described.

Keywords
Cynaropicrin; Derivatization; Guaianolide; SAR; Trypanosoma brucei.