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

Anna Galkina,Nico Krause,Marcel Kaiser,Mairin Lenz,Thomas J Schmidt,Constantin G Daniliuc

doi:10.3390/molecules24061068

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.

Highlights

In a previous communication, we reported on the identification of furanoheliangolide-type sesquiterpene lactones (STLs) as strong trypanocides with high activity and selectivity againstTrypanosoma brucei rhodesiense, the causative agent of East African Human Typanosomiasis [1].A compound from the aerial parts of Helianthus tuberosus L. (Jerusalem Artichoke; Asteraceae), 4,15-iso-atriplicolide tiglate was found active with an IC50 value as low as 15 nM against the parasite
From the dichloromethane extract obtained from aerial parts of Helianthus tuberosus L. we obtained, by column chromatography on silica followed by preparative HPLC, the known 4,15-iso-atriplicolide tiglate (1) as well as the analogous esters with methacrylic (2) and isobutryric acid (3) [2]
18 units, leading to an elemental formula of C20 H24 O7, indicating the addition of H2 O to 1. This was in agreement with the considerably shorter HPLC retention time of 4 on a C18 column in comparison with the iso-atriplicolide esters

Summary

Introduction

We reported on the identification of furanoheliangolide-type sesquiterpene lactones (STLs) as strong trypanocides with high activity and selectivity againstTrypanosoma brucei rhodesiense, the causative agent of East African Human Typanosomiasis [1].A compound from the aerial parts of Helianthus tuberosus L. (Jerusalem Artichoke; Asteraceae), 4,15-iso-atriplicolide tiglate was found active with an IC50 value as low as 15 nM against the parasite. We reported on the identification of furanoheliangolide-type sesquiterpene lactones (STLs) as strong trypanocides with high activity and selectivity against. Trypanosoma brucei rhodesiense, the causative agent of East African Human Typanosomiasis [1]. A compound from the aerial parts of Helianthus tuberosus L. (Jerusalem Artichoke; Asteraceae), 4,15-iso-atriplicolide tiglate was found active with an IC50 value as low as 15 nM against the parasite. In an attempt to isolate a higher quantity of this STL, as well as further related compounds from this plant, we found, besides the mentioned tiglate, the methacrylate and isobutyrate analogues. Molecules 2019, 24, 1068 along with a further, hitherto undescribed STL. We report on the structure elucidation, as well as the results of antiprotozoal tests of this new STL and the hitherto untested 4,15-iso-atriplicolide esters

Methods

Results

Conclusion