Antimalarial activity of the alkaloid, heptaphylline, and the furanocoumarin, imperatorin, from Clausena anisata against human Plasmodium falciparum malaria: Ex vivo trophozoitocidal, schizonticidal and gametocytocidal approach

Background: The erythrocytic stage life cycle of the malaria parasite, Plasmodium falciparum, consists of trophozoite, schizont and gametocyte stages in humans. Various antimalarial agents target different stages of the parasite to produce treatment outcomes. This study reports on the stage specific antimalarial activity of heptaphylline and imperatorin against human P. falciparum in addition to their cytotoxicity and selectivity indices (SI). Methods: The compounds were isolated from Clausena anisata using column chromatography and their structures elucidated using NMR spectroscopy. The antimalarial activity was determined by measuring the trophozoitocidal, schizonticidal and gametocytocidal activities of the compounds using the SYBR green assay. Cytotoxicity was evaluated using the tetrazolium-based colorimetric assay. Results: Heptaphylline and imperatorin produced trophozoitocidal, schizonticidal and gametocytocidal activities with IC 50 s of 1.57 (0.2317) - 26.92 (0.3144) µM with those of artesunate (the standard drug) being 0.00024 (0.0036) - 0.0070 (0.0013) µM. In the cytotoxicity assay, the compounds produced CC 50S greater than 350 µM and SI of 13.76 - 235.90. Also, the trophozoitocidal and schizonticidal activities of the compounds were more pronounced than their gametocytocidal activity. Imperatorin was 42.04% more trophozoitocidal than hepthaphyline. But, hepthaphyline has more schizonticidal and gametocytocidal properties than imperatorin. Conclusion: Heptaphylline and imperatorin are therefore, promising antimalarial agents since, they possessed potent anti-malaria activity with weak cytotoxicity on RBCs. However, imperatorin is a better antimalaria prophylactic agent whereas heptaphylline is a better malaria treatment agent.