Anti-trypanosomal Activity of Helenalin and Some Structurally Related Sesquiterpene Lactones

 

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Abstract

The anti-trypanosomal activity of six sesquiterpene lactones (helenalin, mexicanin I, 11α,13-dihydrohelenalin acetate, chamissonolide, ivalin and isoalantolactone) against the African Trypanosoma brucei rhodesiense and American T. cruzi was investigated. All tested compounds were found active towards both parasites, the former being generally more sensitive. Helenalin was the most active compound in the series with IC₅₀ values of 0.051 and 0.695 μM against T. brucei rhodesiense and T. cruzi, respectively. The low IC₅₀ value for T. b. rhodesiense indicates that helenalin type compounds may be interesting candidates for further evaluation.

• 1 Picman A K. Biological activities of sesquiterpene lactones.  Biochem. Syst. Ecol.. 1986;  14 255-81
  PubMedGoogle Scholar
• 2 Schmidt T J. Toxic activities of sesquiterpene lactones - structural and biochemical aspects.  Current Org Chem.. 1999;  3 577-605
  PubMedGoogle Scholar
• 3 Fournet A, Munoz V, Roblot F, Hocquemiller R, Cave A, Gantier J C. Antiprotozoal activity of dehydrozaluzanin C, a sesquiterpene lactone isolated from Munnozia maronii (Asteraceae).  Phytother. Res.. 1993;  7 111-5
  PubMedGoogle Scholar
• 4 Grael C F, Vichnewski W, Souza G E, Lopes J L, Albuquerque S, Cunha W R. A study of the trypanocidal and analgesic properties from Lychnophora granmongolense (Duarte) Semir & Leitao Filho.  Phytother. Res.. 2000;  14 203-6
  CrossrefPubMedGoogle Scholar
• 5 Kupchan S M, Eakin M A, Thomas A M. Tumor Inhibitors. 69. Structure-cytotoxicicity relationships among the sesquiterpene lactones.  J. Med. Chem.. 1971;  14 1147-52
  CrossrefPubMedGoogle Scholar
• 6 Schmidt T J. Quantitative structure-cytotoxicity relationships within a series of helenanolide type sesquiterpene lactones.  Pharm. Pharmacol. Lett.. 1999;  9 9-13
  PubMedGoogle Scholar
• 7 Mehlhorn H e ditor. Encyclopedic reference of parasitology. Berlin, Heidelberg; Springer 2001
  Google Scholar
• 8 Willuhn G, Merfort I, Paßreiter C M, Schmidt T J. Chemistry and Systematics of the Genus Arnica . In: Hind DJN, Jeffrey C, Pope GV editors Advances in Compositae Systematics. Kew; Royal Botanic Gardens 1994: 167-95
  Google Scholar
• 9 Baltz T, Baltz D, Giroud C, Crockett J. Cultivation in a semi-defined medium of animal infective forms of Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense .  EMBO J.. 1985;  4 1273-7
  PubMedGoogle Scholar
• 10 Räz B, Iten M, Grether-Bühler Y, Kaminsky R, Brun R. The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T.b. rhodesiense and T.b. gambiense) in vitro .  Acta Trop.. 1997;  68 139-47
  CrossrefPubMedGoogle Scholar
• 11 Hills M, Hudson C, Smith P G. Global monitoring of the resistance of the malarial parasites to drugs: statistical treatment of the micro-test data. WHO, WHO Working paper No. 2.8.5 1986
  Google Scholar
• 12 Croft S L, Urbina J A, Brun R. Chemotherapy of human leishmaniasis and trypanosomiasis. In: Hide G, Mottram JC, Coombs GH, Holmes PH, editors Trypanosomiasis and Leishmaniasis. CAB International 1997: P. 245-57
  Google Scholar

Priv.-Doz. Dr. Thomas J. Schmidt

Institut für Pharmazeutische Biologie

Heinrich-Heine-Universität Düsseldorf

Universitätsstrasse 1, Geb. 26.23

40225 Düsseldorf, Germany

Phone: +49-211-8114179

Fax: +49-211-8111923

Email: e-mail: schmidtt@uni-duesseldorf.de