Terpenes Arrest Parasite Development and Inhibit Biosynthesis of Isoprenoids inPlasmodium falciparum

• DOI: 10.1128/aac.48.7.2502-2509.2004
• Publication Date: 2004-06-23T22:18:08Z
• Authors: Herbert Rodrigues...; Emília A. Kimura; Valnice J. Peres; Alicia S. Couto; Fulgencio A. Aqui...; Alejandro M. Katzin
• Keywords: Terpene; Farnesyl pyrophosphate; Dolichol; Mevalonic acid; Nerolidol; Mevalonate pathway

ABSTRACT Development of new drugs is one the strategies for malaria control. The biosynthesis several isoprenoids in Plasmodium falciparum was recently described. Interestingly, some intermediates and final products biosynthesized by this pathway mammals differ from those P. . These facts prompted us to evaluate various terpenes, molecules with a similar chemical structure pathway, as potential antimalarial drugs. Different terpenes S -farnesylthiosalicylic acid were tested on cultures intraerythrocytic stages , 50% inhibitory concentrations each found: farnesol, 64 μM; nerolidol, 760 nM; limonene, 1.22 mM; linalool, 0.28 acid, 14 μM. All inhibited dolichol trophozoite schizont when [1-( n )- 3 H]farnesyl pyrophosphate triammonium salt ([ H]FPP) used precursor. Farnesol, linalool showed stronger activity isoprenic side chain benzoquinone ring ubiquinones stage. Treatment led decrease intensity band corresponding p21 ras protein. effect both isoprenylation proteins appears be specific, because overall protein not affected. Combinations or work other drugs, like fosmidomycin, could strategy treatment malaria.