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
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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
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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
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Volumen: | 48
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Número: | 7
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Página de inicio: | 2502
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Página de fin: | 2509
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DOI: |
http://dx.doi.org/10.1128/AAC.48.7.2502-2509.2004 |
Título revista: | Antimicrobial Agents and Chemotherapy
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Título revista abreviado: | Antimicrob. Agents Chemother.
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ISSN: | 00664804
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CODEN: | AMACC
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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
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00664804_v48_n7_p2502_Goulart |
Referencias:
- Braun-Breton, C., Jendoubi, M., Brunet, E., Perrin, L., Scaife, J., Pereira Da Silva, L., In vivo time course of synthesis and processing of major schizont membrane polypeptides in Plasmodium falciparum (1986) Mol. Biochem. Parasitol., 20, pp. 33-43
- Chojnacki, T., Dallner, G., The biological role of dolichol (1988) Biochem. J., 251, pp. 1-9
- Correll, C.C., Ng, L., Edwards, P.A., Identification of farnesol as the non-sterol derivative of mevalonic acid required for the accelerated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (1994) J. Biol. Chem., 269, pp. 17390-17393
- Couto, A.S., Kimura, E.A., Peres, V.J., Uhrig, M.L., Katzin, A.M., Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum: Presence of dolichols of 11 and 12 isoprene units (1999) Biochem. J., 341, pp. 629-637
- Cowan, M.M., Plant products as antimicrobial agents (1999) Clin. Microbiol. Rev., 12, pp. 564-582
- Crowell, P.L., Prevention and therapy of cancer by dietary monoterpenes (1999) J. Nutr., 129, pp. 775S-778S
- De Macedo, C.S., Uhrig, M.L., Kimura, E.A., Katzin, A.M., Characterization of the isoprenoid chain of coenzyme Q in Plasmodium falciparum (2002) FEMS Microbiol. Lett., 207, pp. 13-20
- Desjardins, R.E., Canfield, C.J., Haynes, J.D., Chulay, J.D., Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique (1979) Antimicrob. Agents Chemother., 16, pp. 710-718
- Dewick, P.M., The biosynthesis of C5-C25 terpenoid compounds (1999) Nat. Prod. Rep., 16, pp. 97-130
- Dewick, P.M., The biosynthesis of C5-C25 terpenoid compounds (2002) Nat. Prod. Rep., 19, pp. 181-222
- Do Socorro, S.R.M.S., Mendonca-Filho, R.R., Bizzo, H.R., De Almeida Rodrigues, I., Soares, R.M., Souto-Padron, T., Alviano, C.S., Lopes, A.H., Antileishmanial activity of a linalool-rich essential oil from Croton cajucara (2003) Antimicrob. Agents Chemother., 47, pp. 1895-1901
- Duker-Eshun, G., Jaroszewski, J.W., Asomaning, W.A., Oppong-Boachie, F., Olsen, C.E., Christensen, S.B., Antiplasmodial activity of labdanes from Aframomum latifolium and Aframomum sceptrum (2002) Planta Med., 68, pp. 642-644
- Eckstein-Ludwig, U., Webb, R.J., Van Goethem, I.D., East, J.M., Lee, A.G., Kimura, M., O'Neill, P.M., Krishna, S., Artemisinins target the SERCA of Plasmodium falciparum (2003) Nature, 424, pp. 957-961
- Egozi, Y., Weisz, B., Gana-Weisz, M., Ben-Baruch, G., Kloog, Y., Growth inhibition of ras-dependent tumors in nude mice by a potent rasdislodging antagonist (1999) Int J. Cancer, 80, pp. 911-918
- Elad, G., Paz, A., Haklai, R., Marciano, D., Cox, A., Kloog, Y., Targeting of K-Ras 4B by S-trans, trans-farnesyl thiosalicylic acid (1999) Biochim. Biophys. Acta, 1452, pp. 228-242
- Gana-Weisz, M., Halaschek-Wiener, J., Jansen, B., Elad, G., Haklai, R., Kloog, Y., The Ras inhibitor S-trans, trans-farnesylthiosalicylic acid chemosensitizes human tumor cells without causing resistance (2002) Clin. Cancer Res., 8, pp. 555-565
- Gardner, M.J., Hall, N., Fung, E., White, O., Berriman, M., Hyman, R.W., Carlton, J.M., Barrell, B., Genome sequence of the human malaria parasite Plasmodium falciparum (2002) Nature, 419, pp. 498-511
- Goldstein, J.L., Brown, M.S., Regulation of the mevalonate pathway (1990) Nature, 343, pp. 425-430
- Haklai, R., Weisz, M.G., Elad, G., Paz, A., Marciano, D., Egozi, Y., Ben-Baruch, G., Kloog, Y., Dislodgment and accelerated degradation of Ras (1998) Biochemistry, 37, pp. 1306-1314
- Holstein, S.A., Hohl, R.J., Monoterpene regulation of Ras and Ras-related protein expression (2003) J. Lipid Res., 44, pp. 1209-1215
- Jomaa, H., Wiesner, J., Sanderbrand, S., Altincicek, B., Weidemeyer, C., Hintz, M., Turbachova, L., Beck, E., Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs (1999) Science, 285, pp. 1573-1576
- Kawata, S., Nagase, T., Yamasaki, E., Ishiguro, H., Matsuzawa, Y., Modulation of the mevalonate pathway and cell growth by pravastatin and d-limonene in a human hepatoma cell line (Hep G2) (1994) Br. J. Cancer, 69, pp. 1015-1020
- Kellogg, B.A., Poulter, C.D., Chain elongation in the isoprenoid biosynthetic pathway (1997) Curr. Opin. Chem. Biol., 1, pp. 570-578
- Kessler, S.W., Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbent: Parameters of the interaction of antibody-antigen complexes with protein A (1975) J. Immunol., 115, pp. 1617-1624
- Kimura, E.A., Couto, A.S., Peres, V.J., Casal, O.L., Katzin, A.M., N-linked glycoproteins are related to schizogony of the intraerythrocytic stage in Plasmodium falciparum (1996) J. Biol. Chem., 271, pp. 14452-14461
- Laemmli, U.K., Cleavage of structural proteins during the assembly of the head of bacteriophage T4 (1970) Nature, 227, pp. 680-685
- Lopes, N.P., Kato, M.J., Andrade, E.H., Maia, J.G., Yoshida, M., Planchart, A.R., Katzin, A.M., Antimalarial use of volatile oil from leaves of Virola surinamensis (Rol.) Warb. by Waiapi Amazon Indians (1999) J. Ethnopharmacol., 67, pp. 313-319
- Marciano, D., Ben-Baruch, G., Marom, M., Egozi, Y., Haklai, R., Kloog, Y., Farnesyl derivatives of rigid carboxylic acids-inhibitors of ras-dependent cell growth (1995) J. Med. Chem., 38, pp. 1267-1272
- Moura, I.C., Wunderlich, G., Uhrig, M.L., Couto, A.S., Peres, V.J., Katzin, A.M., Kimura, E.A., Limonene arrests parasite development and inhibits isoprenylation of proteins in Plasmodium falciparum (2001) Antimicrob. Agents Chemother., 45, pp. 2553-2558
- Palmer, D.N., Husbands, D.R., Winter, P.J., Blunt, J.W., Jolly, R.D., Ceroid lipofuscinosis in sheep. I. Bis(monoacylglycerol)phosphate, dolichol, ubiquinone, phospholipids, fatty acids, and fluorescence in liver lipopigment lipids (1986) J. Biol. Chem., 261, pp. 1766-1772
- Pasvol, G., Wilson, R.J., Smalley, M.E., Brown, J., Separation of viable schizont-infected red cells of Plasmodium falciparum from human blood (1978) Ann. Trop. Med. Parasitol., 72, pp. 87-88
- Pattnaik, S., Subramanyam, V.R., Bapaji, M., Kole, C.R., Antibacterial and antifungal activity of aromatic constituents of essential oils (1997) Microbios, 89, pp. 39-46
- Pouter, C.D., Wiggins, P.L., Plummer, T.L., Isolation and assay of dolichol and dolichyl phosphate (1981) J. Org. Chem., 46, pp. 1532-1533
- Rohmer, M., The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants (1999) Nat. Prod. Rep., 16, pp. 565-574
- Sacchettini, J.C., Poulter, C.D., Creating isoprenoid diversity (1997) Science, 277, pp. 1788-1789
- Shi, W., Gould, M.N., Induction of differentiation in neuro-2A cells by the monoterpene perillyl alcohol (1995) Cancer Lett., 95, pp. 1-6
- Trager, W., Jensen, J.B., Human malaria parasites in continuous culture (1976) Science, 193, pp. 673-667
- Utzinger, J., Tanner, M., Singer, B.H., The Internet: A valuable tool for Roll Back Malaria (2001) Trends Parasitol., 17, pp. 159-161
- Vial, H.J., Isoprenoid biosynthesis and drug targeting in the Apicomplexa (2000) Parasitol. Today, 16, pp. 140-141
- Vial, H.J., Ancelin, M.L., Philippot, J.R., Thuet, M.J., Biosynthesis and dynamics of lipids in Plasmodium-infected mature mammalian erythrocytes (1990) Blood Cells, 16, pp. 531-561
- Wang, K.C., Ohnuma, S., Isoprenyl diphosphate synthases (2000) Biochim. Biophys. Acta, 1529, pp. 33-48
- Wiesner, J., Henschker, D., Hutchinson, D.B., Beck, E., Jomaa, H., In vitro and in vivo synergy of fosmidomycin, a novel antimalarial drug, with clindamycin (2002) Antimicrob. Agents Chemother., 46, pp. 2889-2894
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