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Interestingly, some intermediates and final products biosynthesized by this pathway in mammals differ from those biosynthesized in<jats:italic>P. falciparum<\/jats:italic>. These facts prompted us to evaluate various terpenes, molecules with a similar chemical structure to the intermediates of the isoprenoids pathway, as potential antimalarial drugs. Different terpenes and<jats:italic>S<\/jats:italic>-farnesylthiosalicylic acid were tested on cultures of the intraerythrocytic stages of<jats:italic>P. falciparum<\/jats:italic>, and the 50% inhibitory concentrations for each one were found: farnesol, 64 \u03bcM; nerolidol, 760 nM; limonene, 1.22 mM; linalool, 0.28 mM; and<jats:italic>S<\/jats:italic>-farnesylthiosalicylic acid, 14 \u03bcM. All the terpenes tested inhibited dolichol biosynthesis in the trophozoite and schizont stages when [1-(<jats:italic>n<\/jats:italic>)-<jats:sup>3<\/jats:sup>H]farnesyl pyrophosphate triammonium salt ([<jats:sup>3<\/jats:sup>H]FPP) was used as precursor. Farnesol, nerolidol, and linalool showed stronger inhibitory activity on the biosynthesis of the isoprenic side chain of the benzoquinone ring of ubiquinones in the schizont stage. Treatment of schizont stages with<jats:italic>S<\/jats:italic>-farnesylthiosalicylic acid led to a decrease in intensity of the band corresponding a p21<jats:italic><jats:sup>ras<\/jats:sup><\/jats:italic>protein. The inhibitory effect of terpenes and<jats:italic>S<\/jats:italic>-farnesylthiosalicylic acid on the biosynthesis of both dolichol and the isoprenic side chain of ubiquinones and the isoprenylation of proteins in the intraerythrocytic stages of<jats:italic>P. falciparum<\/jats:italic>appears to be specific, because overall protein biosynthesis was not affected. Combinations of some terpenes or<jats:italic>S<\/jats:italic>-farnesylthiosalicylic acid tested in this work with other antimalarial drugs, like fosmidomycin, could be a new strategy for the treatment of malaria.<\/jats:p>","DOI":"10.1128\/aac.48.7.2502-2509.2004","type":"journal-article","created":{"date-parts":[[2004,6,23]],"date-time":"2004-06-23T22:18:08Z","timestamp":1088029088000},"page":"2502-2509","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":128,"title":["Terpenes Arrest Parasite Development and Inhibit Biosynthesis of Isoprenoids in<i>Plasmodium falciparum<\/i>"],"prefix":"10.1128","volume":"48","author":[{"given":"Herbert","family":"Rodrigues Goulart","sequence":"first","affiliation":[{"name":"Departamento de Parasitologia, Instituto de Cie\u0302ncias Biome\u0301dicas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi\u0301lia A.","family":"Kimura","sequence":"additional","affiliation":[{"name":"Departamento de Parasitologia, Instituto de Cie\u0302ncias Biome\u0301dicas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valnice J.","family":"Peres","sequence":"additional","affiliation":[{"name":"Departamento de Parasitologia, Instituto de Cie\u0302ncias Biome\u0301dicas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia S.","family":"Couto","sequence":"additional","affiliation":[{"name":"Departamento de Engenharia Meca\u0304nica, Escola Polite\u0301cnica, Universidade de Sa\u0303o Paulo, Sa\u0303o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulgencio A.","family":"Aquino Duarte","sequence":"additional","affiliation":[{"name":"CIHIDECAR, Departamento de Qui\u0301mica Orga\u0301nica. 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