Specialized antiplasmodial secondary metabolites from Aspergillus niger 58, an endophytic fungus from Terminalia...

Terminalia catappa L. (West Indian-Almond) is a medicinal plant used in traditional medicine for the treatment of infectious diseases. Moreover, various organic extracts prepared from this plant have been reported to exhibit antiplasmodial activity.

The need for new antimalarials is still an urgency driven by the alarmingly high burden of malaria in endemic regions, with multitude of people dying annually. We have previously identified an endophytic fungus Aspergillus niger 58 harboured by T. catappa as having promising specialized secondary metabolites against the malaria parasites. In the present study, we report the antiplasmodial activity-guided chromatographic isolation of some metabolites secreted by this endophytic fungus.

The SYBR Green I-based fluorescence microtiter plate assay was used to monitor the growth of Plasmodium falciparum parasites in culture in the presence and absence of inhibitors and results were validated by microscopic analysis of Giemsa-stained culture smears. Giemsa-stain microscopy was also used to study the cell cycle stage-specific action of selected fractions.

The results revealed that the multidimensional purification of the crude extract (IC₅₀: 4.03 μg/mL) provided RPHPLC F17 (IC₅₀: 0.09 μg/mL) and RPHPLC F18 (IC₅₀: 0.1 μg/mL) with activity against P. falciparum 3D7 (Pf3D7) strain. Moreover, both fractions at IC₉₉ (0.5 μg/mL) exhibited multi-stages action by targeting all the three stages of the life cycle of blood-stage Pf3D7. Two compounds, flavasperone (1) and aurasperone A (2) were isolated, of which aurasperone A exhibited good potency against Pf3D7 (IC₅₀: 4.17 μM) and P. falciparum INDO (PfINDO) (IC₅₀: 3.08 μM).

Our study adds credence to the notion that endophytic extracts are potential storehouses for potent specialized secondary metabolites that can be harnessed to fight the malaria parasite and reduce the burden of this disease worldwide. An endophyte that can be cultured in laboratory with ability to secrete promising metabolites of medicinal value holds the promise of conserving Nature from the threat of annihilation of flora for medicinal purposes.