Malaria, an infectious disease that kills more than 438,000 people per year worldwide, is a major public health problem. The emergence of strains resistant to conventional therapeutic agents necessitates the discovery of new drugs. We previously demonstrated that various substances, including terpenes, have antimalarial activity in vitro and in vivo. Nerolidol is a sesquiterpene present as an essential oil in several plants that is used in scented products and has been approved by the US Food and Drug Administration as a food-flavouring agent. In this study, the antimalarial activity of nerolidol was investigated in a mouse model of malaria. Mice were infected with Plasmodium berghei ANKA and were treated with 1000 mg/kg/dose nerolidol in two doses delivered by the oral or inhalation route. In mice treated with nerolidol, parasitaemia was inhibited by >99% (oral) and >80% (inhalation) until 14 days after infection (P <0.0001). On Day 30 post-infection, the survival rate of orally treated mice was 90% compared with 16% in controls (P <0.0001). In contrast, inhalation-treated mice showed a survival rate of 50% vs. 42% in controls (P > 0.05). The toxicity of nerolidol administered by either route was not significant, whilst genotoxicity was observed only at the highest dose tested. These results indicate that combined use of nerolidol and other drugs targeting different points of the same isoprenoid pathway may be an effective treatment for malaria.
A fact which favors the increase in morbidity and mortality of malaria cases in the world is the resistance to chemotherapeutic agents that the parasite presents. Therefore, it is necessary to identify new potential targets specific to the parasite in order to be able to perform a rational planning. One target for the evaluation of potential antimalarial compounds is isoprenoid synthesis, which occurs via the 2-C-methyl-d-erythritol-4-phosphate pathway in Plasmodium falciparum. Several intermediaries and final products of this pathway were identified in the parasite and lead us to the conclusion that it is different from the vertebrate host. In this chapter, we describe the effect of some monoterpenes and sesquiterpenes on Plasmodium falciparum and Plasmodium berghei as potential antimalarial drugs.
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