1. Reversal of chloroquine and mefloquine resistance in Plasmodium falciparum by the two monoindole alkaloids, icajine and isoretuline.
- Author
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Frédérich M, Hayette MP, Tits M, De Mol P, and Angenot L
- Subjects
- Alkaloids chemistry, Alkaloids isolation & purification, Alkaloids toxicity, Animals, Colon cytology, Drug Resistance, Multiple, Drug Synergism, Humans, Indoles chemistry, Indoles isolation & purification, Indoles toxicity, Inhibitory Concentration 50, Molecular Structure, Plasmodium falciparum growth & development, Strychnine analogs & derivatives, Strychnine chemistry, Strychnine isolation & purification, Strychnine toxicity, Tumor Cells, Cultured, Alkaloids pharmacology, Antimalarials pharmacology, Chloroquine pharmacology, Indoles pharmacology, Mefloquine pharmacology, Plasmodium falciparum drug effects, Strychnine pharmacology
- 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 (IC(50) > 10 microM or 5 microg/ml). Nevertheless, three alkaloids (icajine, isoretuline and strychnobrasiline) did reverse chloroquine resistance at concentrations between 2.5 and 25 microg/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).
- Published
- 2001
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