In vitro and in vivo Antimalarial Properties of Isostrychnopentamine, an Indolomonoterpenic Alkaloid from Strychnos usambarensis

Michel Frédérich; Monique Tits; Eric Goffin; Geneviève Philippe; Philippe Grellier; Patrick De Mol; Marie-Pierre Hayette; Luc Angenot

doi:10.1055/s-2004-827151

Planta Medica, Inhaltsverzeichnis

Planta Med 2004; 70(6): 520-525
DOI: 10.1055/s-2004-827151

Original Paper

Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

In vitro and in vivo Antimalarial Properties of Isostrychnopentamine, an Indolomonoterpenic Alkaloid from Strychnos usambarensis

Michel Frédérich¹ ^, ² , Monique Tits¹ , Eric Goffin¹ , Geneviève Philippe¹ , Philippe Grellier³ , Patrick De Mol² , Marie-Pierre Hayette² , Luc Angenot¹

¹Natural and Synthetic Drug Research Center, Laboratory of Pharmacognosy, University of Liège, Liège, Belgium
²Laboratory of Medical Microbiology, University of Liège, Liège, Belgium
³Laboratoire de Biologie parasitaire, USM 0504, Département RDDM, Muséum National d'Histoire Naturelle, Paris, France

This research was supported by the Belgian National Fund for Scientific Research (FNRS) (grant No 3 453 201 and fellowship for M.F.)

Abstract

Isostrychnopentamine (ISP) is an asymmetric indolomonoterpenic alkaloid isolated from the leaves of Strychnos usambarensis. The in vitro antiplasmodial activities against five Plasmodium falciparum cell lines were evaluated: ISP possessed an in vitro IC₅₀ near 0.1 μM against all P. falciparum cell lines tested (chloroquine-resistant and chloroquine-sensitive lines) and showed antiplasmodial selectivity compared to cytotoxicity on human cell lines. The stage-dependent susceptibility to a short exposure of ISP was then investigated. The ring stage was shown to be the most sensitive one, but all stages were affected by ISP treatment. By means of fluorescence microscopy, it was shown that ISP was not accumulated inside the food vacuole of the parasite. Finally, the in vivo antimalarial activities against the P. berghei NK173 and P. vinckei petteri murine strains were determined. The ED₅₀ in vivo was about 30 mg/kg/day by the intraperitoneal route (after 4 days treatment).

Key words

Plasmodium falciparum - Plasmodium berghei - Plasmodium vinckei - isostrychnopentamine - Strychnos usambarensis - Loganiaceae

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Referenzen

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Michel Frédérich

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Natural and Synthetic Drug Research Center

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