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Planta Med 2001; 67(6): 523-527
DOI: 10.1055/s-2001-16476
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Reversal of Chloroquine and Mefloquine Resistance in Plasmodium falciparum by the Two Monoindole Alkaloids, Icajine and Isoretuline

Michel Frédérich1, 2,*, Marie-Pierre Hayette2 , Monique Tits1 , Patrick De Mol2 , Luc Angenot1
  • 1 Laboratoire de Pharmacognosie, Institut de Pharmacie, Université de Liège, Belgium
  • 2 Laboratoire de Microbiologie Médicale, Institut de Pathologie, Université de Liège, Belgium
Further Information

Publication History

August 18, 2000

December 2, 2000

Publication Date:
17 August 2001 (online)

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Abstract

Eight naturally occurring monoindole alkaloids were evaluated in vitro for their ability to inhibit Plasmodium falciparum growth and, in drug combination, to reverse the resistance of a chloroquine-resistant strain of Plasmodium falciparum. None of these indole alkaloids has significant intrinsic antiplasmodial activity (IC50 > 10 μM or 5 μg/ml). Nevertheless, three alkaloids (icajine, isoretuline and strychnobrasiline) did reverse chloroquine resistance at concentrations between 2.5 and 25 μg/ml (IF of 12.82 for isoretuline on W2 strain). The Interaction Factor (IF) equals 2, < 2, or > 2 for additive, antagonistic or synergistic effects of alkaloids on chloroquine inhibition, respectively. Icajine and isoretuline were also assessed in vitro for their mefloquine potentiating activity on a mefloquine-resistant strain of Plasmodium falciparum. Only icajine proved to be synergistic with mefloquine (IF = 15.38).

Key words

Plasmodium falciparum - chloroquine - mefloquine - indole alkaloid

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Michel Frédérich

Laboratoire de Pharmacognosie

Institut de Pharmacie

Université de Liège

Avenue de l’hôpital 1

CHU du Sart Tilman, B36, tour 4

4000 Liège

Belgium

Email: M.Frederich@ulg.ac.be

Fax: +32 4 366 43 32