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 p ractically devoid of intrinsic in vitro and in vivo antimalarial activ ity. However, when combined with CQ at a dose level much lower than th eir IC50 value, they markedly enhanced in vitro the effectiveness of t he synthetic drug against a CQ-resistant strain of Plasmodium falcipar um. 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 strychnobrasil ine (1) and malagashanine (2), together with four minor alkaloids, wer e isolated. Strychnobrasiline and malagashanine were devoid of both in trinsic antimalarial activity and cytotoxicity effect, but exhibited s ignificant CQ-potentiating actions. These findings could account for t he above-mentioned empirical use of S. myrtoides. The present state of research on antimalarial drug from Strychnos genus is also discussed.