Thirty-three N-acyl 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized. For these ozonides, weak base functional groups were not required for high antimalarial potency against Plasmodium falciparum in vitro, but were necessary for high antimalarial efficacy in Plasmodium berghei-infected mice. A wide range of Log P/DpH 7.4 values were tolerated, although more lipophilic ozonides tended to be less metabolically stable.
These findings show that cytoadherence, a potential pathogenic property of P. falciparum infected red blood cells, continues long after the parasite has been killed.
Evaporative precipitation of nanosuspension (EPN) was used to fabricate nanoparticles of a poorly water-soluble antimalarial drug, artemisinin (ART), with the aim of enhancing its dissolution rate. We investigated the nanoparticle fabrication of ART via a full factorial experimental design considering the effects of drug concentration and solvent to antisolvent ratio on the physical, morphological and dissolution properties of ART.
Plasmodium falciparum resistance to chloroquine and sulphadoxine–pyrimethamine has led to the recent adoption of artemisinin-based combination therapies (ACTs) as the first line of treatment against malaria. ACTs comprise semisynthetic artemisinin derivatives paired with distinct chemical classes of longer acting drugs. These artemisinins are exceptionally potent against the pathogenic asexual blood stages of Plasmodium parasites and also act on the transmissible sexual stages.
Almost one million people die of severe malaria every year. In recent years, artemisinin-based combination therapies have become the backbone of the treatment of uncomplicated falciparum malaria and have helped to reduce the burden of malaria in large parts of the malaria-endemic world. However, the treatment of severe malaria,the clinical syndrome responsible for most malaria-associated deaths, remains largely unaffected by this development.
Artemisinin has been used effectively in malaria treatment. With the emerging resistance to malaria, the optimum and judicial use of the drug has become important.