| Summary: | <p>Abstract</p> <p>Background</p> <p>Discovering new lead compounds against malaria parasites is a crucial step to ensuring a sustainable global pipeline for effective anti-malarial drugs. As far as we know, no previous phytochemical or pharmacological investigations have been carried out on <it>Sorindeia juglandifolia.</it> This paper describes the results of an anti-malarial activity-driven investigation of the fruits of this Cameroonian plant.</p> <p>Methods</p> <p>Air-dried fruits were extracted by maceration using methanol. The extract was fractionated by flash chromatography followed by column chromatography over silica gel, eluting with gradients of hexane-ethyl acetate mixtures. Resulting fractions and compounds were tested <it>in vitro</it> against the <it>Plasmodium falciparum</it> chloroquine-resistant strain W2, against field isolates of <it>P. falciparum</it>, and against the <it>P. falciparum</it> recombinant cysteine protease falcipain-2. Promising fractions were assessed for acute toxicity after oral administration in mice. One of the promising isolated compounds was assessed <it>in vivo</it> against the rodent malaria parasite <it>Plasmodium berghei</it>.</p> <p>Results</p> <p>The main end-products of the activity-guided fractionation were 2,3,6-trihydroxy benzoic acid (1) and 2,3,6-trihydroxy methyl benzoate (2). Overall, nine fractions tested against <it>P. falciparum</it> W2 and falcipain-2 were active, with IC<sub>50</sub> values of 2.3-11.6 μg/ml for W2, and 1.1-21.9 μg/ml for falcipain-2. Purified compounds (1) and (2) also showed inhibitory effects against <it>P. falciparum</it> W2 (IC50s 16.5 μM and 13.0 μM) and falcipain-2 (IC50s 35.4 and 6.1 μM). In studies of <it>P. falciparum</it> isolates from Cameroon, the plant fractions demonstrated IC<sub>50</sub> values of 0.14-19.4 μg/ml and compounds (1) and (2) values of 6.3 and 36.1 μM. <it>In vivo</it> assessment of compound (1) showed activity against <it>P. berghei</it> strain B, with mean parasitaemia suppressive dose and curative dose of 44.9 mg/kg and 42.2 mg/kg, respectively. Active fractions were found to be safe in mice after oral administration of 7 g/kg body weight.</p> <p>Conclusions</p> <p>Fractions of <it>Sorindeia juglandifolia</it> and two compounds isolated from these fractions were active against cultured malaria parasites, the <it>P. falciparum</it> protease falcipain-2, and in a rodent malaria model. These results suggest that further investigation of the anti-malarial activities of natural products from <it>S. juglandifolia</it> will be appropriate.</p>
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