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Planta Med 2012; 78(6): 553-556
DOI: 10.1055/s-0031-1298241
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Cynaropicrin: The First Plant Natural Product with In Vivo Activity against Trypanosoma brucei

Stefanie Zimmermann1 , 2 , Marcel Kaiser2 , Reto Brun2 , Matthias Hamburger1 , Michael Adams1
  • 1Department of Pharmaceutical Sciences, Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland
  • 2Swiss Tropical and Public Health Institute, Basel, Switzerland
Further Information

Publication History

received Nov. 9, 2011 revised January 9, 2012

accepted January 16, 2012

Publication Date:
13 February 2012 (online)

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Abstract

A screen of 1800 plant and fungal extracts with subsequent HPLC-based activity profiling was done to identify new antiprotozoal leads from nature. This led to the identification of cynaropicrin (1) from the herb Centaurea salmantica L. (Asteraceae) as a potent in vitro inhibitor of Trypanosoma brucei rhodesiense. It preferentially inhibited T. b. rhodesiense (IC50 of 0.3 µM) and T. brucei gambiense (IC50 of 0.2 µM), compared to Trypanosoma cruzi (IC50 of 4.4 µM) and Plasmodium falciparum (IC50 of 3.0 µM). Testing against melarsoprol- and pentamidine-resistant strains (IC50s of 0.3 µM and 0.1 µM, respectively) showed no cross-resistance. Intraperitoneal administration of 2 × 10 mg/kg body weight/day in the T. b. rhodesiense STIB 900 acute mouse model led to a 92 % reduction of parasitemia compared to untreated controls on day seven post-infection. Removal of the 2-hydroxymethyl-2-propenoyl moiety of cynaropicrin led to a loss of toxicity towards T. b. rhodesiense. Cytotoxicities against rat myoblasts (L6 cells), human colon adenocarcinoma cells, and murine peritoneal macrophages were measured, and selectivity indices of 7.8, 62, and 9.5 were determined. This is the first report of a plant natural product with potent in vivo activity against Trypanosoma brucei.

Key words

Centaurea salmantica L. - Asteraceae - antitrypanosomal - human African trypanosomiasis (HAT) - Trypanosoma brucei rhodesiense - sesquiterpene lactone - cynaropicrin

Supporting Information

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Dr. Michael Adams

Department of Pharmaceutical Sciences
University of Basel

Klingelbergstrasse 50

4056 Basel

Switzerland

Phone: +41 6 12 67 15 64

Fax: +41 6 12 67 14 74

Email: michael.adams@unibas.ch

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