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Description
Malaria continues to pose a serious global health threat and remains one of the leading causes of morbidity and mortality in sub-Saharan Africa, affecting millions of people. Despite ongoing efforts to control the disease and the availability of antimalarial therapies, the rise in resistance to frontline antimalarial drugs has exacerbated the health burden in these regions, urging the need for novel therapeutic compounds. With nature serving as an effective reservoir for novel bioactive molecules, this study focused on Picralima nitida T. Durand & H. Durand, Syll. Fl. Congol. (Apocynaceae), which is indigenous to West Africa and has been used traditionally as an antimalarial. Scientific reports have validated its use with several compounds, most of which are alkaloids, specifically monoterpene indole alkaloids (MIAs) being isolated from it. The antiplasmodial activities of some of these MIAs have been established in chloroquine-sensitive strains of P. falciparum. However, the activity of these compounds against chloroquine-resistant strains of P. falciparum and their drug-like potential remains underexplored.
This study aimed to isolate monoterpene indole alkaloids from P. nitida seeds, evaluate their antiplasmodial activity against both chloroquine-sensitive and -resistant strains of P. falciparum, and assess their basic drug metabolism and pharmacokinetics (DMPK) profiles
One new compound, isopicranitine (6) and nine known monoterpene indole alkaloids: Betaine methylester formate (1), N-methylpseudoakuammigine (2), N -methylakuammine (3), Ajmalicine (4), 3-isoajmalicine (5), Akuammine(7), Akuammidine(8), Akuammigine (9) and Pseudoakuammigine (10a) and Pseudoakuammigine N-oxide (10b) were successfully isolated from the seeds of Picralima nitida. Structure elucidation was done by analysis of their MS and NMR spectroscopic data. Most compounds showed moderate antiplasmodial effects against the chloroquine-sensitive P. falciparum strains. Three of them (1, 7, and 9) showed good activity with pXC50 > 5 against the resistant strains of the parasite. The compounds exhibited favourable LogD and aqueous solubility properties, providing insights into their drug-likeness.
This study confirms the antiplasmodial potential of MIAs from P.nitida and provides preliminary pharmacokinetic data that support the promise as potential lead compounds. These findings contribute to natural product-based drug discovery efforts and highlight the relevance of medicinal plants in addressing drug-resistant malaria