The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors lovastatin and simvastatin inhibit the in vitro intraerythrocytic development of Plasmodium falciparum and Babesia divergens, with concentrations inhibiting parasite growth by 50% in the ranges of 10 to 20 and 5 to 10 ug -ml-', respectively. For P.falciparum, the 50% inhibitory concentrations were in the same range whatever the chloroquine susceptibility of the strains tested (strain F32/Tanzania [chloroquine susceptible] or FcB.1/Columbia [resistant]). The stage-dependent susceptibility of P. falciparum to simvastatin was studied by subjecting synchronized cultures to 6-h pulses of drug throughout the 48-h erythrocytic life cycle. The most important inhibitory effects were observed between the 12th and 30th hours of the cycle, corresponding to the trophozoite stage. This period precedes the S phase and the nuclear divisions. Parasites in the newly formed ring stage (time zero to the 6th hour of the cycle) and the schizont stage (30th to 48th hour of the cycle) were weakly or not susceptible to simvastatin pulses.The Apicomplexa hemoparasites Plasmodium falciparum and Babesia divergens, the causative agents of human malaria and bovine babesiosis, respectively, still constitute major health and economic problems in most developing countries (12,24). The (8,21,22) and depend on their import from the host's plasma. With the use of a serum-free medium, we have recently found a unidirectional transfer of phospholipids from human high-density lipoproteins to the intraerythrocytic P. falciparum by ducts and vesicles moving from the erythrocyte to the parasitophorous vacuole membranes (6). A similar phospholipid transfer was observed in B. divergensinfected erythrocytes (RBC), but no ducts or vesicles were observed (21). High-density lipoproteins support the in vitro growth of B. divergens and P. falciparum in the absence of other major serum components and appeared to be a lipid source for the parasites (6,7,21 by P. falciparum-infected RBC, we have shown evidence for an isoprenoid metabolisnm until, at least, the farnesyl PPi step (16).This pathway, with numerous end products, is essential for various cellular functions such as mitochondrial electron transport, tRNA synthesis, control of cell growth, protein glycosylation, and intracellular targeting (4). In both prokaryotic and eukaryotic cells, the isoprenoid pathway is highly regulated through feedback regulations at the level of two sequential enzymes involved in the synthesis of mevalonate: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and HMGCoA reductase (4). HMG-CoA reductase inhibitors are available as hypocholesterolemic agents in humans. The goal of our study was to establish whether the HMG-CoA reductase inhibitors lovastatin and simvastatin are able to inhibit the in vitro development of P. falciparum and B. divergens. MATERIALS AND METHODSLovastatin and simvastatin, both in the lactone form, were kindly provided by J. C. Mazi&re (Hopital St-Antoine, Paris, France) and by C. Fous...

Cryptolepis sanguinolenta extracts are currently used by African herbalists to cure malaria but the compounds involved in its antimalarial activity have not been identified. Two alkaloids, cryptolepine and isocryptolepine, have been isolated from the roots of C. sanguinolenta and their antimalarial activity evaluated. Both alkaloids possess intrinsic inhibitory activity against the human malaria parasite, Plasmodium falciparum in vitro, whatever the chloroquine‐resistance status of the strains used. Cryptolepine was slightly more efficient for parasite killing with an IC50 in the range of 0.2 to 0.6 μMSC compared with an IC50 of about 0.8 μMSC for isocryptolepine. The antimalarial activity of cryptolepine was confirmed in vivo on the rodent malarial parasites Plasmodium vinckei petteri and Plasmodium berghei ANKA.

Cryptolepis sanguinolenta extracts are currently used by African herbalists to cure malaria but the compounds involved in its antimalarial activity have not been identified. Two alkaloids, cryptolepine and isocryptolepine, have been isolated from the roots of C. sunguinolenta and their antimalarial activity evaluated. Both alkaloids possess intrinsic inhibitory activity against the human malaria parasite, Plasmodium fakiparum in vitro, whatever the chloroquine-resistance status of the strains used. Cryptolepine was slightly more efficient for parasite killing with an ICs in the range of 0.2 to 0.6 p~ compared with an ICso of about 0.8 PM for isocryptolepine. The antimalarial activity of cryptolepine was confirmed in vivo on the rodent malarial parasites Plasmodium vinckei petleri and Plasmodium berghei ANKA.

Blood-parasite protozoa are causative agents of some of the major tropical or infectious diseases for humans and animals, such as Plasmodium for malaria (about 270 million infected people), Trypanosoma cruzi for Chagas' disease (about 18-20 million individuals), African trypanosomes for human and bovine trypanosomiasis, and Babesia for cattle and dogs. The absence of efficient vaccines against these diseases, the absence or the high toxicity of the few drugs against American and African trypanosomiasis, and the emergence of chemoresistance against Plasmodium falciparum emphasize the necessity to propose new antiparasitic strategies. Among these strategies, the biological strategy is based on the identification of key molecules for parasite development such that structural analogs can be designed that are parasite-specific or sufficiently inactive for the host. This requires a careful biochemical analysis of each step of the parasite life cycle. For blood-parasite protozoa, the lipid metabolism required for membrane biogenesis, antimicrotubular drugs or inhibitors of the mitotic spindle, and drug targeting offer new trends in chemotherapy against Plasmodium, Babesia, and trypanosomes.