In Vitro and in Vivo Chloroquine-Potentiating Action of Strychnos myrtoides Alkaloids Against Chloroquine-Resistant Strains of Plasmodium Malaria

Abstract

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 anti-malarial 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 anti-malarial 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 anti-malarial drug from Strychnos genus is also discussed.

Key words

Strychnos myrtoides - Loganiaceae - anti-malarial activity - chloroquine potentiation - indole alkaloids - strychnobrasiline - malagashanine