In vitro and in vivo chloroquine-potentiating action of Strychnos myrtoides alkaloids against chloroquine-resistant strains of Plasmodium malaria.
Crude alkaloids of Strychnos myrtoides Gilg & Busse, empirically used as an adjuvant to chloroquine (CQ) in Malagasy herbal remedies, were practically devoid of intrinsic in vitro and in vivo antimalarial activity. However, when combined with CQ at a dose level much lower than their IC50 value, they markedly enhanced in vitro the effectiveness of the synthetic drug against a CQ-resistant strain of Plasmodium falciparum. They also enhanced in vivo CQ activity against a resistant strain of Plasmodium yoelii. By counter-current distribution (CCD) separation of the crude alkaloid extract, the two major alkaloids strychnobrasiline (1) and malagashanine (2), together with four minor alkaloids, were isolated. Strychnobrasiline and malagashanine were devoid of both intrinsic antimalarial activity and cytotoxicity effect, but exhibited significant CQ-potentiating actions. These findings could account for the above-mentioned empirical use of S. myrtoides. The present state of research on antimalarial drug from Strychnos genus is also discussed.
Rasoanaivo
P
P
Institut Malgache de Recherches Appliquées, Antananarivo, Madagascar.
Ratsimamanga-Urverg
S
S
Milijaona
R
R
Rafatro
H
H
Rakoto-Ratsimamanga
A
A
Galeffi
C
C
Nicoletti
M
M
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance; D004357:Drug Synergism; D006367:HeLa Cells; D006801:Humans; D008270:Madagascar; D016778:Malaria, Falciparum / Q000188:drug therapy; D051379:Mice; D010946:Plants, Medicinal; D010963:Plasmodium falciparum / Q000187:drug effects*; D010967:Plasmodium yoelii / Q000187:drug effects*
D000470:Alkaloids; D000962:Antimalarials; C103769:malagashanine; C103767:strychnobrasiline; D002738:Chloroquine