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Planta Med 2004; 70(5): 407-413
DOI: 10.1055/s-2004-818967
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Alkaloids from Cassytha filiformis and Related Aporphines: Antitrypanosomal Activity, Cytotoxicity, and Interaction with DNA and Topoisomerases

Sara Hoet1 , 5 , Caroline Stévigny1 , 5 , Sébastien Block1 , Frederik Opperdoes2 , Pierre Colson3 , Brigitte Baldeyrou4 , Amélie Lansiaux4 , Christian Bailly4 , Joëlle Quetin-Leclercq1
  • 1Laboratoire de Pharmacognosie, Unité d’Analyse Chimique et Physico-Chimique des Médicaments, Université Catholique de Louvain, Bruxelles, Belgium
  • 2Research Unit for Tropical Diseases, Christian de Duve Institute of Cellular Pathology and Laboratory of Biochemistry, Catholic University of Louvain, Brussels, Belgium
  • 3Biospectroscopy and Physical Chemistry Unit, Department of Chemistry and Natural and Synthetic Drugs Research Centre, University of Liège, Liège, Belgium
  • 4INSERM U-524 et Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, IRCL, Lille, France
  • 5These authors contributed equally to this study
This research was supported by the Belgian National Fund for Scientific Research (fellowship to S.H.), by a grant from the ”Fonds Spécial de Recherche” of the Catholic University of Louvain (fellowship to S.B.) and the Ligue Nationale Contre le Cancer (grant to C.B.). Support by the ”Actions Intégrées Franco-Belges” Programme Tournesol is acknowledged (to C.B. and P.C.).
Further Information

Publication History

Received: October 27, 2003

Accepted: February 7, 2004

Publication Date:
04 May 2004 (online)

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Abstract

Cassytha filiformis (Lauraceae), a widely distributed parasitic plant, contains several aporphine alkaloids and is often used in African folk medicine to treat cancer, African trypanosomiasis and other diseases. In a previous investigation, we showed that the alkaloid plant extract and the isolated aporphines possessed in vitro cytotoxic properties. In this paper, we evaluated the in vitro activity of the alkaloid extract (IC50 = 2.2 μg/mL) and its three major aporphine alkaloids (actinodaphnine, cassythine, and dicentrine) on Trypanosoma brucei brucei as well as four related commercially available aporphines (bulbocapnine, glaucine, isocorydine, boldine). Only the three alkaloids from Cassytha filiformis were active on the trypanosomes in vitro (IC50 = 3 - 15 μM). Additionally, we compared the cytotoxicity of these seven compounds on HeLa cells. Glaucine was the most cytotoxic compound on HeLa cells (IC50 = 8.2 μM) in the series. In order to elucidate their mechanism of action, the binding mode of these molecules to DNA was studied by UV absorption, circular and linear dichroism spectroscopy. The results of the optical measurements indicated that all seven aporphines effectively bind to DNA and behave as typical intercalating agents. Biochemical experiments showed that actinodaphnine, cassythine and dicentrine also interfere with the catalytic activity of topoisomerases in contrast to the four other aporphines. These interactions with DNA may explain, at least in part, the effects observed on cancer cells and on trypanosomes.

Key words

Aporphine alkaloids - DNA interaction - Cassytha filiformis - Lauraceae - topoisomerase inhibition - antitrypanosomal activity - cytotoxicity

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Prof. J. Quetin-Leclercq

Laboratoire de Pharmacognosie

Unité CHAM

UCL 72.30

Avenue E. Mounier 72

1200 Brussels

Belgium

Fax: +32-2-764-72-53

Email: leclercq@cham.ucl.ac.be