In vitro and in vivo antimalarial properties of isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis.
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 IC (50) near 0.1 microM 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 ED (50) in vivo was about 30 mg/kg/day by the intraperitoneal route (after 4 days treatment).
Frédérich
Michel
M
Natural and Synthetic Drug Research Center, Laboratory of Pharmacognosy, University of Liège, Avenue de l'hôpital 1,B36, 4000 Liège, Belgium. M.Frederich@ulg.ac.be
Tits
Monique
M
Goffin
Eric
E
Philippe
Geneviève
G
Grellier
Philippe
P
De Mol
Patrick
P
Hayette
Marie-Pierre
MP
Angenot
Luc
L
D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002243:Carbolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects; D004351:Drug Resistance; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D051379:Mice; D021261:Parasitic Sensitivity Tests; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects*; D031451:Strychnos; D013729:Terpenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000470:Alkaloids; D000962:Antimalarials; D002243:Carbolines; D010936:Plant Extracts; D013729:Terpenes; C473210:isostrychnopentamine