Antitrypanosomal Activity of Sesquiterpene Lactones from Helianthus tuberosus L. Including a New Furanoheliangolide with an Unusual Structure

Abstract

As part of our efforts to exploit the antitrypanosomal potential of sesquiterpene lactones (STL) from Helianthus tuberosus L. (Asteraceae), besides the known 4,15-iso-atriplicolide tiglate, -methacrylate and -isobutyrate, a hitherto unknown STL was isolated. Its structure was solved by extensive NMR measurements and confirmed by single crystal X-ray crystallography. This novel compound is a structural analog 4,15-iso-atriplicolide tiglate that possesses the same basic furanoheliangolide skeleton but differs in the position of the oxo function which is at C-2 instead of C-1, as well as in the fact that the oxygen atom of the furanoid ring is part of a hemiketal structure at C-3 and a double bond between C-5 and C-6. For this new STL we propose the name heliantuberolide-8-O-tiglate. Its activity against Trypanosoma brucei rhodesiense (causative agent of East African Human Typanosomiasis, Trypanosoma cruzi (Chagas Disease), Leishmania donovani (Visceral Leishmaniasis) and Plasmodium falciparum (Tropical Malaria) as well as cytotoxicity against rat skeletal myoblasts (L6 cell line) was determined along with those of the hitherto untested 4,15-iso-atriplicolide methacrylate and isobutyrate. In comparison with the iso-atriplicolide esters, the new compound showed a much lower level of bioactivity.

Keywords

• sesquiterpene lactone
• furanoheliangolide
• X-ray crystallography
• antiprotozoal activity
• Trypanosoma brucei rhodesiense
• Trypanosoma cruzi
• Leishmania donovani
• Plasmodium falciparum
• cytotoxicity