Stage -specific antimalarial activity of alkaloidal fractions of the Avicennia africana P. Beauv. (Avicenniaceae) leaf extract

Background: The global call for malaria eradication rested on finding drugs that not only act against asexual but also sexual forms of the parasite. This study evaluates the stage-specific anti-malarial and cytotoxic activities of the fractions of crude alkaloidal extracts from Avicennia africana leaves. Methods: The crude and alkaloidal extracts (AAA and AAQ) from A. africana were fractionated using column chromatography and further analyzed using GC-mass spectroscopy. The fractions were then tested for antimalarial activity against the trophozoites, schizonts, and gametocyte stages of chloroquine-sensitive strains of 3D7 P. falciparum using the SYBR Green 1 assay. The cytotoxic effects of the fractions were evaluated using the MTT-based assay. Results: The fractions AAA1-AAA5 and AAQ1-AAQ5 produced promising trophozoitocidal activities with an IC50 value range of 0.399–45.690 µg/mL, with the artesunate yielding 0.09x103 µg/mL. The schizonticidal and gametocytocidal activities of selected fractions demonstrated high potency with IC50s of 0.622–18.820 µg/mL against artesunate with 1.800x10-3 and 5.100x10-3 µg/mL, respectively. The cytotoxic effect of fractions produced CC50 that was higher than 100 µg/mL with negligible cytotoxicity on erythrocytes and SI that ranged from 2.189 to 280.899. The major compounds identified in fractions AAA1, AAQ1, and AAQ2 are 8-carbomoylquinoline, razoxane, and dexrazoxane respectively. Conclusion: The fractions exhibited promising trophozoitocidal, schizonticidal, and gametocytocidal effects, with no significant cytotoxic effects on RBCs. Quinoline-based alkaloids and iron chelators in this plant are implicated as possible lead-compound transmission blockers of the parasite.