ArticleAntimicrobial agents and chemotherapy2004
Terpenes arrest parasite development and inhibit biosynthesis of isoprenoids in Plasmodium falciparum.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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56 citing papers in PubMed, 159 citations in OpenAlex.
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- Antiparasitic effect of Farnesol against Leishmania major: A rationale from in vitro and in silico investigations.PloS one · 2023Article
- Evaluation of farnesol orally and topically against experimental cutaneous leishmaniasis: In -vivo analysis.PloS one · 2023Article
- Fractions 14 and 36K of Metabolite ExtractInfection and drug resistance · 2023Article
- The Biomedical Importance of the Missing Pathway for Farnesol and Geranylgeraniol Salvage.Molecules (Basel, Switzerland) · 2022Review
- Novel Formula of Antiprotozoal Mixtures.Antibiotics (Basel, Switzerland) · 2022Article
- Menthol carbonates as potent antiparasitic agents: synthesis and in vitro studies along with computer-aided approaches.BMC complementary medicine and therapies · 2022Article
- Antiparasitic effects ofSaudi journal of biological sciences · 2022Article
- Preparation and Characterization of Blank and Nerolidol-Loaded Chitosan-Alginate Nanoparticles.Nanomaterials (Basel, Switzerland) · 2022Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Development of new drugs is one of the strategies for malaria control. The biosynthesis of several isoprenoids in Plasmodium falciparum was recently described. Interestingly, some intermediates and final products biosynthesized by this pathway in mammals differ from those biosynthesized in P. falciparum. 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 S-farnesylthiosalicylic acid were tested on cultures of the intraerythrocytic stages of P. falciparum, and the 50% inhibitory concentrations for each one were found: farnesol, 64 microM; nerolidol, 760 nM; limonene, 1.22 mM; linalool, 0.28 mM; and S-farnesylthiosalicylic acid, 14 microM. All the terpenes tested inhibited dolichol biosynthesis in the trophozoite and schizont stages when [1-(n)-(3)H]farnesyl pyrophosphate triammonium salt ([(3)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 S-farnesylthiosalicylic acid led to a decrease in intensity of the band corresponding a p21(ras) protein. The inhibitory effect of terpenes and S-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 P. falciparum appears to be specific, because overall protein biosynthesis was not affected. Combinations of some terpenes or S-farnesylthiosalicylic acid tested in this work with other antimalarial drugs, like fosmidomycin, could be a new strategy for the treatment of malaria.
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