Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-23T17:45:14.589Z Has data issue: false hasContentIssue false
  • English
  • Français

In vitro anti-trypanosomal activity of elatol isolated from red seaweed Laurencia dendroidea

Published online by Cambridge University Press:  14 June 2010

P. VEIGA-SANTOS ,
K. J. PELIZZARO-ROCHA ,
A. O. SANTOS ,
T. UEDA-NAKAMURA ,
B. P. DIAS FILHO ,
S. O. SILVA ,
D. B. SUDATTI ,
E. M. BIANCO ,
R. C. PEREIRA  and
C. V. NAKAMURA
P. VEIGA-SANTOS
Affiliation:
Programa de Pós-graduação em Ciências Farmacêuticas, Laboratório de Inovação Tecnológica no Desenvolvimento de Fármacos e Cosméticos, Bloco B-08, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil
K. J. PELIZZARO-ROCHA
Affiliation:
Programa de Pós-graduação em Microbiologia, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, PR 445, Km 380, CEP 86051-990, Campus Universitário, Londrina, Paraná, Brazil
A. O. SANTOS
Affiliation:
Programa de Pós-graduação em Microbiologia, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, PR 445, Km 380, CEP 86051-990, Campus Universitário, Londrina, Paraná, Brazil
T. UEDA-NAKAMURA
Affiliation:
Programa de Pós-graduação em Ciências Farmacêuticas, Laboratório de Inovação Tecnológica no Desenvolvimento de Fármacos e Cosméticos, Bloco B-08, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil
B. P. DIAS FILHO
Affiliation:
Programa de Pós-graduação em Ciências Farmacêuticas, Laboratório de Inovação Tecnológica no Desenvolvimento de Fármacos e Cosméticos, Bloco B-08, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil
S. O. SILVA
Affiliation:
Programa de Pós-graduação em Ciências Farmacêuticas, Laboratório de Inovação Tecnológica no Desenvolvimento de Fármacos e Cosméticos, Bloco B-08, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil
D. B. SUDATTI
Affiliation:
Departamento de Biologia Marinha, Universidade Federal Fluminense, Caixa Postal 100644, CEP 24001-970, Niterói, Rio de Janeiro, Brazil
E. M. BIANCO
Affiliation:
Programa de Pós-graduação em Quimica Orgânica, Universidade Federal Fluminense, Outiero de São João Baptista, s/n°, CEP 24.020-150, Niterói, Rio de Janeiro, Brazil
R. C. PEREIRA
Affiliation:
Departamento de Biologia Marinha, Universidade Federal Fluminense, Caixa Postal 100644, CEP 24001-970, Niterói, Rio de Janeiro, Brazil
C. V. NAKAMURA*
Affiliation:
Programa de Pós-graduação em Ciências Farmacêuticas, Laboratório de Inovação Tecnológica no Desenvolvimento de Fármacos e Cosméticos, Bloco B-08, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil
*
*Corresponding author: Programa de Pós-graduação em Ciências Farmacêuticas, Laboratório de Inovação Tecnológica no Desenvolvimento de Fármacos e Cosméticos, Bloco B-08, Universidade Estadual de Maringá, Av. Colombo 5790, CEP 87020-900, Maringá, Paraná, Brazil. Tel: +55 44 3041 5012. Fax: +55 44 3261 4860. E-mail: cvnakamura@uem.br
Get access Rights & Permissions [Opens in a new window]

Summary

Chagas' disease is a debilitating but comparatively neglected illness that affects about 15 million people. There is an urgent need to develop new, more effective, and less-toxic compounds. In this study, we assessed the in vitro anti-trypanosomal activity of the sesquiterpene elatol from the Brazilian red seaweed Laurencia dendroidea. We used electron microscopy to evaluate the effect of elatol on the morphology and ultrastructure of the parasite. Elatol showed a dose-dependent effect against the epimastigote, trypomastigote, and amastigote forms, with IC50 values of 45·4, 1·38, and 1·01 μm, respectively. Observation of treated intracellular amastigotes by light microscopy demonstrated a total elimination of the infection at a dose of 3·0 μm. In addition, the compound did not affect the red blood cells, and the CC50 value for LLCMK2 cells was 27·0 μm. Transmission and scanning electron micrographs showed aberrant-shaped cells and breaks in the plasma membrane, prominent swollen mitochondria, and extensive formation of cytoplasmic vacuoles in all the forms. This is the first report of the anti-trypanosomal effect of the sesquiterpene elatol.

Keywords

Trypanosoma cruziLaurencia dendroideaelatolanti-trypanosomal activitymitochondrion
Type
Research Article
Information
Parasitology , Volume 137 , Issue 11 , September 2010 , pp. 1661 - 1670
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Bansemira, A., Justa, N., Michalikb, M., Lindequista, U. and Lalk, M. (2004). Extracts and sesquiterpene derivatives from the red alga Laurencia chondrioides with antibacterial activity against fish and human pathogenic bacteria. Chemistry and Biodiversity 1, 463–467.CrossRefGoogle Scholar
Brener, Z. (1962). Therapeutic activity and criterion of cure on mice experimentally infected with Trypanosoma cruzi. Revista do Instituto de Medicina tropical de São Paulo 4, 389–396.Google ScholarPubMed
Camargo, E. P. (1964). Growth and differentiation in Trypanosoma cruzi. Origen of metacyclic trypanosomes in liquid media. Revista do Instituto de Medicina tropical de São Paulo 6, 93–100.Google Scholar
Cassano, V. (2009). Taxonomia e filogenia do complexo Laurencia (Ceramiales, Rhodophyta), com ênfase no estado do Rio de Janeiro, Brasil. Ph.D. thesis. Instituto de Botânica da Secretaria de Estado do Meio Ambiente, São Paulo.Google Scholar
Coura, J. R. and Castro, S. L. (2002). A critical review on Chagas disease chemotherapy. Memórias do Instituto Oswaldo Cruz 97, 3–24.CrossRefGoogle Scholar
Da Gama, B. A. P., Pereira, R. C., Soares, A. R., Teixeira, V. L. and Yoneshigue-Valentin, Y. (2003). Is the mussel test a good indicator of antifouling activity? A comparison between laboratory and field assays. Biofouling 19, 161–169.CrossRefGoogle Scholar
Dantas, A. P., Salomão, K., Barbosa, H. S. and Castro, S. L. (2006). The effect of Bulgarian propolis against Trypanosoma cruzi and during its interaction with host cells. Memórias do Instituto Oswaldo Cruz 101, 207–211.CrossRefGoogle ScholarPubMed
de Nys, R., Leya, T., Maximilien, R., Afsar, A., Nair, P. S. R. and Steinberg, P. D. (1996). The need of standardised broad scale biossay testing: a case study using the red algae Laurencia rigida. Biofouling 10, 213–224.CrossRefGoogle Scholar
Freile-Pelegrin, Y., Robledo, D., Chan-Bacab, M. J. and Ortega-Morales, B. O. (2008). Antileishmanial properties of tropical marine algae extracts. Fitoterapia 79, 374–377. doi: 10.1016/j.fitote.2008.02.006.CrossRefGoogle ScholarPubMed
Hay, M. E., Fenical, W. and Gustafson, K. (1987). Chemical-defense against diverse coral-reef herbivores. Ecology 68, 1581–1591.CrossRefGoogle ScholarPubMed
Hay, M. E., Duffy, J. E. and Fenical, W. (1988). Seaweed chemical defenses: among-compound and among-herbivore variance. Proceedings of the 6th International Coral Reef Symposium 3, 43–48.Google Scholar
Iliopoulou, D., Roussis, V., Pannecouque, C., De Clercq, E. and Vagias, C. (2002). Halogenated sesquiterpenes from the red alga Laurencia obtusa. Tetrahedron 58, 6749–6755. doi: 10.1016/S0040-4020(02)00687-7.CrossRefGoogle Scholar
Izumi, E., Morello, L. G., Ueda-Nakamura, T., Yamada-Ogatta, S. F.; Dias-Filho, B. P., Cortez, D. A. G., Ferreira, I. C. P., Morgado-Días, J. A. and Nakamura, C. V. (2008). Trypanosoma cruzi: antiprotozoal activity of parthenolide obtained from Tanacetum parthenium (L.) Schultz Bip. (Asteraceae, Compositae) against epimastigote and amastigote forms. Experimental Parasitology 118, 324–330. doi:10.1016/j.exppara.2007.08.015.CrossRefGoogle ScholarPubMed
Kang, J. Y., Khan, M. N. A., Park, N. H., Cho, J. Y., Lee, M. C., Fujii, H. and Hong, Y. K. (2008). Antipyretic, analgesic, and anti-inflammatory activities of the seaweed Sargassum fulvellum and Sargassum thunbergii in mice. Journal of Ethnopharmacology 116, 187–190. doi: 10.1016/j.jep.2007.10.032.CrossRefGoogle ScholarPubMed
Kladi, M., Vagias, C., Stavri, M., Rahman, M. M., Gibbons, S. and Roussis, V. (2008). C15 acetogenins with antistaphylococcal activity from the red alga Laurencia glandulifera. Phytochemistry Letters 1, 31–36. doi: 10.1016/j.phytol.2007.12.004.CrossRefGoogle Scholar
König, G. M. and Wright, A. D. (1997). Sesquiterpene content of the antibacterial dichlormethane extract of the red alga Laurencia obtusa. Planta Medica 63, 186–187. doi: 10.1055/S-2006-957643.CrossRefGoogle Scholar
Luize, P. S., Tiuman, T. S., Morello, L. G., Maza, P. K., Ueda-Nakamura, T., Dias-Filho, B. P., Cortez, D. A. G., Mello, J. C. P. and Nakamura, C. V. (2005). Effects of medicinal plant extracts on growth of Leishmania (L.) amazonensis and Trypanosoma cruzi. Brazilian Journal of Pharmaceutical Sciences 41, 85–94.Google Scholar
Luize, P. S., Ueda-Nakamura, T., Dias-Filho, B. P., Cortez, D. A. G. and Nakamura, C. V. (2006). Activity of neolignans isolated from Piper regnellii (MIQ.) C. DC. var. pallescens (C. DC.) YUNCK against Trypanosoma cruzi. Biological Pharmaceutical Bulletin 29, 2126–2130.CrossRefGoogle ScholarPubMed
Matsuhiro, B., Conte, A. F., Damonte, E. B., Kolender, A. A., Matulewicz, M. C., Mejías, E. G., Pujol, C. A. and Zúñiga, E. A. (2005). Structural analysis and antiviral activity of a sulfated galactan from the red seaweed Schizymenia binderi (Gigartinales, Rhodophyta). Carbohydrate Research 340, 2392–2402. doi:10.1016/j.carres.2005.08.004.CrossRefGoogle ScholarPubMed
Mayer, A. M. S., Rodríguez, A. D., Berlinck, R. G. S. and Hamann, M. T. (2009). Marine pharmacology in 2005–6: Marine compounds with anthelmintic, antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems, and other miscellaneous mechanisms of action. Biochimica et Biophysica Acta 1790, 283–308. doi: 10.1016/j.bbagen.2009.03.011.CrossRefGoogle ScholarPubMed
Mendiola-Martínez, J., Hernández, H., Acuña, D., Esquivel, M., Scull, , Lizama, R. and Abreu-Payrol, J. (2005). Inhibiting activity of the in vitro growth of Plasmodium falciparum of extracts from algae of genus Laurencia. Revista Cubana de Medicina Tropical 57, 192–195.Google ScholarPubMed
Menezes, D., Valentim, C., Oliveira, M. F. and Vannier-Santos, M. A. (2006). Putrescine analogue cytotoxicity against Trypanosoma cruzi. Parasitology Research 98, 99–105. doi: 10.1007/S00436-005-0010-1.CrossRefGoogle ScholarPubMed
Menna-Barreto, R. F. S., Corrêa, J. R., Pinto, A. V., Soares, M. J. and Castro, S. L. (2007). Mitochondrial disruption and DNA fragmentation in Trypanosoma cruzi induced by naphthoimidazoles synthesized from β-lapachone. Parasitology Research 101, 895–905. doi: 10.1007/s00436-007-0556-1.CrossRefGoogle ScholarPubMed
Menna-Barreto, R. F. S., Gonçalves, R. S. L., Costa, E. M., Silva, R. S. F., Pinto, A. V., Oliveira, M. F. and de Castro, S. L. (2009). The activity on Trypanosoma cruzi of novel synthetic naphthoquinones is mediated by mitochondrial dysfunction. Free Radical Biology and Medicine 47, 644–653. doi: 10.1016/j.freeradbiomed.2009.06.004.CrossRefGoogle ScholarPubMed
Moo-Puc, R., Robledo, D. and Freile-Pelegrin, Y. (2008). Evaluation of selected tropical seaweeds for in vitro anti-trichomonal activity. Journal of Ethnopharmacology 120, 92–97. doi: 10.1016/j.jep.2008.07.035.CrossRefGoogle ScholarPubMed
Moreira, D. R. M., Leite, A. C. L., Santos, R. R. and Soares, M. B. P. (2009). Approaches for the development of new anti-Trypanosoma cruzi agents. Current Drug Targets 10, 212–231.CrossRefGoogle ScholarPubMed
Nara, T., Kamei, Y., Akiko, T., Annoura, T., Hirota, K., Iizumi, K., Dohmoto, Y., Ono, T. and Aoki, T. (2005). Inhibitory action of marine algae extracts on the Trypanosoma cruzi dihydroorotate dehydrogenase activity and on the protozoan growth in mammalian cells. Parasitology International 54, 59–64. doi: 10.1016/j.parint.2004.11.001.CrossRefGoogle ScholarPubMed
Orhan, I., Sener, B., Atici, T., Brun, R., Perozzo, R. and Tasdemir, D., (2006). Turkish freshwater and marine macrophyte extracts show in vitro anti-protozoal activity and inhibit FabI, a key enzyme of Plasmodium falciparum fatty acid biosynthesis. Phytomedicine 13, 388–393. doi: 10.1016/j.phymed.2005.10.010.CrossRefGoogle Scholar
Prata, A. (2001). Clinical and epidemiological aspects of Chagas disease. The Lancet Infectious Diseases 1, 91–100. doi: 10.1016/S1473-3099(01)00065-2.CrossRefGoogle ScholarPubMed
Salas, C. A., Tapia, R. A., Ciudad, K., Armstrong, V., Orellana, M., Kemmerling, U., Ferreira, J., Maya, J. D. and Morello, A. (2008). Trypanosoma cruzi: Activities of lapachol and a- and b-lapachone derivatives against epimastigote and trypomastigote forms. Bioorganic & Medicinal Chemistry 16, 668–674. doi:10.1016/j.bmc.2007.10.038.CrossRefGoogle Scholar
Salgado, L. T., Viana, N. B., Andrade, L. R., Leal, R. N., Gama, B. A. P., Attias, M., Pereira, R. C. and Amado Filho, G. M. (2008). Intra-cellular storage, transport and exocytosis of halogenated compounds in marine red alga Laurencia obtusa. Journal of Structural Biology 162, 345–355. doi: 10.1016/j.jsb.2008.01.015.CrossRefGoogle ScholarPubMed
Schaeffer, D. J. and Krylov, V. S. (2000). Anti-HIV activity of extracts and compounds from algae and cyanobacteria. Ecotoxicology and Environmental Safety 45, 208–227. doi: 10.1006/eesa.1999.1862.CrossRefGoogle ScholarPubMed
Schmunis, G. A. (2007). Epidemiology of Chagas disease in non-endemic countries: the role of international migration. Memórias do Instituto Oswaldo Cruz 102, 75–85.CrossRefGoogle ScholarPubMed
Sims, J. J., Lin, G. H. Y. and Wing, R. M. (1974). Marine natural products: elatol, a halogenated sesquiterpene alcohol from the red alga Laurencia elata. Tetrahedron Letters 39, 3487–3490.CrossRefGoogle Scholar
Steinberg, P. D., De Ny, R. and Kjelleberg, S. (1998). Chemical inhibition of epibiota by Australian seaweeds. Biofouling 12, 227–244.CrossRefGoogle Scholar
Sudatti, D. B., Rodrigues, S. V., Coutinho, R., Gama, B. A. P., Salgado, L. T., Amado Filho, G. M. and Pereira, R. C. (2008). Transport and defensive role of elatol at the surface of the red seaweed Laurencia obtusa (CERAMIALES, RHODOPHYTA). Journal of Phycology 44, 584–591. doi: 10.1111/j.1529-8817.2008.00507.X.CrossRefGoogle ScholarPubMed
Tonin, T. D., Barbosa, V. A., Bocca, C. C., Ramos, E. R. F., Nakamura, C. V., Costa, W. F., Basso, E. A., Ueda-Nakamura, T. and Sarragiotto, M. H. (2009). Comparative study of the trypanocidal activity of the methyl 1-nitrophenyl-1,2,3,4-9H-tetrahydro-β-carboline-3-carboxylate derivatives and benznidazole using theoretical calculations and cyclic voltammetry. European Journal of Medicinal Chemistry 44, 1745–1750. doi:10.1016/j.ejmech.2008.03.044.CrossRefGoogle Scholar
Topcu, G., Anydoqmus, Z., Imre, S., Goren, A. C., Pezzuto, J. M., Clement, J. A. and Kingston, D. G. (2003). Brominated sesquiterpenes from the red alga Laurencia obtusa. Journal of Natural Products 66, 1505–1508.CrossRefGoogle ScholarPubMed
Urbina, J. A. and Docampo, R. (2003). Specific chemotherapy of Chagas disease: controversies and advances. TRENDS in Parasitology 19, 495–501. doi:10.1016/j.pt.2003.09.001.CrossRefGoogle ScholarPubMed
Urbina, J. A. (2009). Ergosterol biosynthesis and drug development for Chagas disease. Memórias do Instituto Oswaldo Cruz 104, 311–318.CrossRefGoogle ScholarPubMed
Vairappan, C. S., Suzuki, M., Abe, T. and Masuda, M. (2001). Antibacterial halogenated metabolites from the Malaysian Laurencia species. Phytochemistry 58, 291–297.doi: S0031-9422(01)00260-6.CrossRefGoogle ScholarPubMed
Vairappan, C. S. (2003). Potent antibacterial activity of halogenated metabolites from Malaysian red algae, Laurencia majuscule (Rhodomelaceae, Ceramiales). Biomolecular Engineering 20, 255–259. doi:10.1016/S1389-0344(03)00067-4.CrossRefGoogle Scholar
Valdez, R. H., Tonin, L. T. D., Ueda-Nakamura, T., Dias-Filho, B. P. D., Morgado-Díaz, J. A., Sarragiotto, M. H. and Nakamura, C. V. (2009). Biological activity of 1,2,3,4-tetrahydro-β-carboline-3-carboxamides against Trypanosoma cruzi. Acta Tropica 110, 7–14. doi: 10.1016/j.actatropica.2008.11.008.CrossRefGoogle Scholar
Van-Hellemond, J. J., Opperdoes, F. R. and Tielens, A. G. (2005). The extraordinary mitochondrion and unusual citric acid cycle in Trypanosoma brucei. Biochemical Society Transactions 33, 967–971.CrossRefGoogle ScholarPubMed
Wang, B., Zhang, W., Duan, X. and Li, X. (2009). In vitro antioxidative activities of extract and semi-purified fractions of the marine red alga, Rhodomela confervoides (Rhodomelaceae). Food Chemistry 113, 1101–1105. doi: 10.1016/j.foodchem.2008.08.078.CrossRefGoogle Scholar
WHO/TDR – World Health Organization (2006). Report of the Scientific Working Group on Chagas disease, Buenos Aires, Argentina, p. 7.Google Scholar
Wright, A. D., König, G. M., Angerhofer, C. K., Greenidge, P., Linden, A. and Desqueyroux-Faundez, R. (1996). Anti-malarial activity: the search for marine-derived natural products with selective anti-malarial activity. Journal of Natural Products 59, 710–716.CrossRefGoogle Scholar