Targeting the intra-erythrocytic life cycle of Plasmodium falciparum unveils antimalarial drug discovery starting points from Drymaria cordata and Macaranga monandra.

ETHNOPHARMACOLOGICAL RELEVANCE: Drymaria cordata and Macaranga monandra are two medicinal plants traditionally used in Cameroon to treat malaria, but their scientific validation remains unclear.

AIM OF THE STUDY: To validate the antiplasmodial action of extracts and fractions derived from Drymaria cordata and Macaranga monandra.

MATERIALS AND

METHODS

Aqueous, methanolic, ethanolic, and hydroethanolic extracts of D. cordata (whole plant) and M. monandra (bark) were prepared by maceration followed by liquid-liquid partition of actives. Extracts and fractions were screened against chloroquine-sensitive (Pf3D7) and multidrug-resistant (PfDd2) strains of P. falciparum, while selectivity was determined on Vero cells. Stage-specific analysis and killing dynamics of potent fractions were profiled, complemented with UHPLC-MS analysis coupled to in silico prediction of pharmacokinetics of identified metabolites.

RESULTS

D. cordata ethanolic extract showed moderate activity (IC50PfDd2: 18.9 μg/mL; IC50Pf3D7: 24.51 μg/mL), while all four M. monandra extracts exhibited good activity (IC50 < 8 μg/mL). The methanolic bark extract (MMBME) was highly potent and selective (IC50PfDd2: 2.46 μg/mL, SI > 203; IC50Pf3D7: 1.02 μg/mL, SI > 487). Fractionation yielded two active fractions from MMBME: F2 (IC50PfDd2: 0.60 μg/mL, IC50Pf3D7: 3.42 μg/mL) and F3 (IC50PfDd2: 0.92 μg/mL, IC50Pf3D7: 2.46 μg/mL). Fractions F2 and F3 arrested ring-stage development, lysed trophozoite-infected red blood cells, and blocked merozoite egress. UHPLC-MS analysis identified 17 metabolites in fractions F2 and F3, including fatty acyls, flavonoids, phenols, terpenes, and coumarins. Lecanoric acid was predicted as a promising antimalarial candidate.

CONCLUSIONS

Macaranga monandra bark fractions F2 and F3 are potent sources of antiplasmodial compounds targeting multiple asexual blood stages (ABS).