In Vitroandin VivoChloroquine-Potentiating Action ofStrychnos myrtoidesAlkaloids Against Chloroquine-Resistant Strains ofPlasmodiumMalaria

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 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.

Cascade Annulation Reactions To Access the Structural Cores of Stereochemically Unusual Strychnos Alkaloids

“…Furthermore, it has been shown to restore the activity of CQ against drug-resistant populations of P. falciparun. [5] It is postulated that malagashanine acts by inhibiting a P-glycoprotein efflux pump, similar to those found in multi-drug-resistant cancer cells. Since the discovery of malagashanine, Galeffi and coworkers have identified several other strychnos alkaloids bearing the unusual inverted C-3 stereochemistry [e.g.…”

Medicinal plants: Traditions of yesterday and drugs of tomorrow

“…This led to the isolation of two major bioactive constituents-Strychnobrasiline and Malagashanine (Rasoanaivo et al, 1994) as well as four minor alkaloids. Malagashanine, turned out to be the parent compound of a new subtype of Strychnos alkaloids, the C-21, Nb-secocuran indole alkaloids, isolated so far from the Malagasy Strychnos (Rafatro et al, 2000;Rasoanaivo et al, 2001;Martin et al, 1999).…”

Plant Derived Antimalarial Agents: New Leads and Challenges

“…Strychnos myrtoides is a plant used in Madagascar as an adjuvant with chloroquine for the treatment of malaria. Although the major alkaloid constituents are devoid of activity against malaria parasites, they have been shown to potentiate the action of chloroquine against chloroquine-resistant parasites (Rasoanaivo et al, 1994). The antimalarial action of the Chinese herb Dichroa febrifuga is thought to involve the immune response as it stimulates activated macrophages to produce nitric oxide (Murata, et al, 1998).…”