Plasmodium antiplasmodial activities

Very recently elisapterosin A (30) [18, 19] was found to exhibit strong antiplasmodial activity (IC5010 pg/ml) against Plasmodium falciparum, the parasite responsible for the most severe forms of malaria. 

For the determination of the antiplasmodial activity of the compounds, the multi-resistant Dd2 strain of Plasmodium falciparum was used and [8-3H]-hypoxanthine incorporated into the parasitic nucleic acids measured. The plasmodia were incubated with 0.3% parasitemia and an erythrocyte hematocrit of 2.5% in the presence of different concentrations of selected experimental agents in a final volume of 200 xl. The medium employed was RPMI 1640 containing 10% of heat-treated human serum and 3 mg/1 of gentamycin. In the incubations, the concentrations of the compounds varied from 0.3 to 100 xM. After 48 hours, each batch was treated with 50 xl [8-3H]hypoxanthine and incubated additional 18 hours. Testing results are provided in Table 1. 

Table I. The Main Chemical Constituents and Antiplasmodial Activity of Twenty Essential oils Against Plasmodium falciparum FCM29 strain...

Argemone subfusiformis dried leaves, flowers and seeds were extracted with ethanol-water (70-30%) for 48 h, the aqueous-solution obtained was evaporated under vacuum and the resdue was directly assayed. The antiplasmodial activity was good (24), and extracts were rich in isoquinolleinic Akaloids. In above ground parts, protopine, berberine and allocryptopine were identified (27). According to Sriwilaijaron et al. (28) berberine prevents the development of Plasmodium falciparum by inhibition of its telomerase activity. 

Artemisinin with its crucial endoperoxide bridge is not the only natural compound exhibiting antiplasmodial activity. An example of the biosynthesis of antiplasmodial endoperoxidic compounds is plakortin, a simple 1,2-dioxane derivative, which is produced by the marine sponge Plakortis simplex [93]. This compound shows activity against chloroquine-resistant strains of Plasmodium falciparum (R falciparum) at submicromolar level. 

Interaction of marine isonitriles derivatives with heme was shown to inhibit the transformation of heme into / -hematin and then hemozoin, a polymer produced by Plasmodium in order to neutralize the toxic (detergent-like) free heme produced in the food vacuole. In addition, isonitriles were shown to prevent both the peroxidative and glutathione-mediated destruction of heme under conditions that mimic the environment within the malaria parasite. In summary, isonitriles, similarly to quinoline antimalarials [38], exert their antiplasmodial activity by preventing heme detoxification. 

Tabic 19 In vitro Antiplasmodial Activity of Pterocarpans from Root Bark of E. abyssinica 46 Against Strains VV> and D6of Plasmodium falciparum. 

There have also been reports of antimicrobial activity in this family of alkaloids. AlstiphyUanine B (38), alstiphyllanine C (39), and alstiphyllanine D (40) were reported to have moderate in vitro antiplasmodial activity against Plasmodium falciparum Scholarisin I (60), scholarisin II (61), scholarisin III... 

Harmine and harmaline showed a moderate in vitro antiplasmodial activity against Plasmodium falciparum [97]. 

Trioxaquines have modular structures linking two different moieties. A study of the relation between the structure of the trioxaquines and their antiplasmodial activities in vitro and in vivo was done. All the trioxaquines tested in vitro present interesting antimalarial properties on strains of Plasmodium falciparum chloroquine-sensitive and chloroquine-resistant with ICso inferior to 100 nM and around 10 nM for the best trioxaquines 41). 

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