Anti-trypanosomal cadinanes synthesized by transannular cyclization of the natural sesquiterpene lactone nobilin. Issue 7 (1st April 2015)

• Record Type: Journal Article
• Authors: De Mieri, Maria; Kaiser, Marcel; Brun, Reto; Thormann, Ursula; Imanidis, Georgios; Hamburger, Matthias
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 7(2015)
• Page Start: 1521
• Page End: 1529
• Publication Date: 2015-04-01
• Subjects: STLs sesquiterpene lactones -- DFT density functional theory -- HAT human African trypanosomiasis; Transannular cyclization -- Heliangolide -- Anti-trypanosomal activity -- Sesquiterpene lactones; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.02.005
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Acid-catalyzed transannular cyclization of the germacrene-type sesquiterpene lactone nobilin1 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 ± 1.69 μM). The tricyclic derivative11 showed most potent in vitro activity against Trypanosoma brucei rhodesiense bloodstream forms (IC50 0.46 ± 0.01 μM). Acid-catalyzed transannular cyclization of natural cyclodecadienes is an efficient strategy to generate new natural product derivatives with anti-protozoal activity.