Artículo

Goulart, H.R.; Kimura, E.A.; Peres, V.J.; Couto, A.S.; Duarte, F.A.A.; Katzin, A.M. "Terpenes arrest parasite development and inhibit biosynthesis of isoprenoids in Plasmodium falciparum" (2004) Antimicrobial Agents and Chemotherapy. 48(7):2502-2509
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Abstract:

Development of new drugs is one of the strategies for malaria control. The biosynthesis of several isoprenoids in Plasmodiumfalciparum 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 μM; nerolidol, 760 nM; limonene, 1.22 mM; linalool, 0.28 mM; and S-farnesylthiosalicylic acid, 14 μM. All the terpenes tested inhibited dolichol biosynthesis in the trophozoite and schizont stages when [1-(n)- 3H]farnesyl pyrophosphate triammonium salt ([3H]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 p21ras 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.

Registro:

Documento: Artículo
Título:Terpenes arrest parasite development and inhibit biosynthesis of isoprenoids in Plasmodium falciparum
Autor:Goulart, H.R.; Kimura, E.A.; Peres, V.J.; Couto, A.S.; Duarte, F.A.A.; Katzin, A.M.
Filiación:Departamento de Parasitologia, Instituto de Ciencias Biomedicas, Universidade de São Paulo, São Paulo, Brazil
Departamento de Engenharia Mecanica, Escola Politécnica, Universidade de São Paulo, São Paulo, Brazil
CIHIDECAR, Departamento de Quimica Organica, Universidad de Buenos Aires 1428, Argentina
Universidade de São Paulo, Av. Professor Lineu Prestes, 1374, CEP 05508-900 São Paulo, Brazil
Palabras clave:antimalarial agent; farnesol; farnesylthiosalicylic acid; fosmidomycin; isoprenoid; limonene; linalool; nerolidol; terpene derivative; antimalarial activity; article; biosynthesis; concentration response; controlled study; developmental stage; malaria; malaria control; minimum inhibitory concentration; nonhuman; parasite development; Plasmodium falciparum; priority journal; protein synthesis; schizont; steroidogenesis; trophozoite; Animals; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Depression, Chemical; Dolichol; Electrophoresis, Polyacrylamide Gel; Erythrocytes; Farnesol; Lipid Metabolism; Malaria, Falciparum; Plasmodium falciparum; Precipitin Tests; Salicylic Acids; Terpenes; Ubiquinone
Año:2004
Volumen:48
Número:7
Página de inicio:2502
Página de fin:2509
DOI: http://dx.doi.org/10.1128/AAC.48.7.2502-2509.2004
Título revista:Antimicrobial Agents and Chemotherapy
Título revista abreviado:Antimicrob. Agents Chemother.
ISSN:00664804
CODEN:AMACC
CAS:farnesol, 4602-84-0; fosmidomycin, 66508-37-0, 66508-53-0; limonene, 138-86-3, 5989-27-5; linalool, 78-70-6; nerolidol, 142-50-7, 7212-44-4; Dolichol, 2067-66-5; Farnesol, 4602-84-0; farnesylthiosalicylic acid; Salicylic Acids; Terpenes; Ubiquinone, 1339-63-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00664804_v48_n7_p2502_Goulart

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Citas:

---------- APA ----------
Goulart, H.R., Kimura, E.A., Peres, V.J., Couto, A.S., Duarte, F.A.A. & Katzin, A.M. (2004) . Terpenes arrest parasite development and inhibit biosynthesis of isoprenoids in Plasmodium falciparum. Antimicrobial Agents and Chemotherapy, 48(7), 2502-2509.
http://dx.doi.org/10.1128/AAC.48.7.2502-2509.2004
---------- CHICAGO ----------
Goulart, H.R., Kimura, E.A., Peres, V.J., Couto, A.S., Duarte, F.A.A., Katzin, A.M. "Terpenes arrest parasite development and inhibit biosynthesis of isoprenoids in Plasmodium falciparum" . Antimicrobial Agents and Chemotherapy 48, no. 7 (2004) : 2502-2509.
http://dx.doi.org/10.1128/AAC.48.7.2502-2509.2004
---------- MLA ----------
Goulart, H.R., Kimura, E.A., Peres, V.J., Couto, A.S., Duarte, F.A.A., Katzin, A.M. "Terpenes arrest parasite development and inhibit biosynthesis of isoprenoids in Plasmodium falciparum" . Antimicrobial Agents and Chemotherapy, vol. 48, no. 7, 2004, pp. 2502-2509.
http://dx.doi.org/10.1128/AAC.48.7.2502-2509.2004
---------- VANCOUVER ----------
Goulart, H.R., Kimura, E.A., Peres, V.J., Couto, A.S., Duarte, F.A.A., Katzin, A.M. Terpenes arrest parasite development and inhibit biosynthesis of isoprenoids in Plasmodium falciparum. Antimicrob. Agents Chemother. 2004;48(7):2502-2509.
http://dx.doi.org/10.1128/AAC.48.7.2502-2509.2004