Stage -Specific Antimalarial Activity of Alkaloidal Fractions of the Avicennia africana P. Beauv. (Avicenniaceae) Leaf Extract

Abstract

Background The global call for malaria eradication rested on finding drugs that not only act against asexual but also sexual forms of the parasite. The drawbacks in disease control and prevention due to drug-resistant clones of the parasite piqued our interest in exploring for alternative antimalarial drugs from the mangrove resources. Aims 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 analysed 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 (ref drug) yielding 0.09x10³ µg/mL. The schizonticidal and gametocytocidal activities of selected fractions demonstrated high potency with IC_50s of 0.622–18.820 µg/mL against artesunate (ref drugs) 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 were 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.