Anti-trypanosomal cadinanes synthesized by transannular cyclization of the natural sesquiterpene lactone nobilin

  • Bioorg Med Chem. 2015 Apr 1;23(7):1521-9. doi: 10.1016/j.bmc.2015.02.005.
Maria De Mieri  1 ,  Marcel Kaiser  2 ,  Reto Brun  2 ,  Ursula Thormann  3 ,  Georgios Imanidis  3 ,  Matthias Hamburger  4
Affiliations
  • 1. Department of Pharmaceutical Biology, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland. Electronic address: [email protected].
  • 2. Department of Medical Parasitology & Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, 4000 Basel, Switzerland; University of Basel, Petersplatz 1, 4001 Basel, Switzerland.
  • 3. Institute of Pharma Technology, School of Life Sciences, University of Applied Sciences Northwestern Switzerland, Muttenz, Switzerland.
  • 4. Department of Pharmaceutical Biology, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
PMID: 25740635 DOI: 10.1016/j.bmc.2015.02.005
Abstract

Acid-catalyzed transannular cyclization of the germacrene-type sesquiterpene lactone nobilin 1 was investigated with the aim of obtaining new anti-trypanosomal cadinane derivatives. The reaction was regiospecific in all tested reaction conditions. Compounds were fully characterized by spectroscopic and computational methods, and the anti-trypanosomal activity was evaluated and compared to nobilin (IC50 3.19±1.69μM). The tricyclic derivative 11 showed most potent in vitro activity against Trypanosoma brucei rhodesiense bloodstream forms (IC50 0.46±0.01μM). Acid-catalyzed transannular cyclization of natural cyclodecadienes is an efficient strategy to generate new natural product derivatives with anti-protozoal activity.

Keywords
Anti-trypanosomal activity; Heliangolide; Sesquiterpene lactones; Transannular cyclization.