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Arzneimittelforschung 2009; 59(4): 207-211
DOI: 10.1055/s-0031-1296387
Antibiotics · Antimycotics · Antiparasitics · Antiviral Drugs · Chemotherapeutics · Cytostatics
Editio Cantor Verlag Aulendorf (Germany)

In vitro Effect of a New Cinnamic Acid Derivative Against the Epimastigote Form of Trypanosoma cruzi

Gilberto L Pardo Andreu
1   Departamento de Investigaciones Biomédicas, Centro de Química Farmacéutica, Ciudad de La Habana, (Cuba)
2   Centro de Estudios para las Investigaciones y Evaluaciones Biólogicas, Instituto de Farmacia y Alimentos, Universidad de La Habana, Ciudad Habana, (Cuba)
,
Natalia M Inada
3   Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, (Brasil)
,
Rolando F Pellón
1   Departamento de Investigaciones Biomédicas, Centro de Química Farmacéutica, Ciudad de La Habana, (Cuba)
,
Maite L Docampo
1   Departamento de Investigaciones Biomédicas, Centro de Química Farmacéutica, Ciudad de La Habana, (Cuba)
,
Mirta L Fascio
4   Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, (Argentina)
,
Norma B D’Accorso
4   Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, (Argentina)
,
Anibal E Vercesi
3   Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, (Brasil)
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Publikationsverlauf

Publikationsdatum:
13. Dezember 2011 (online)

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Abstract

An intensive effort has been directed toward finding alternative drugs for treatment of Chagas’ disease, caused by Trypanosoma cruzi (T. cruzi), and prophylaxis of blood in endemic areas. The preparation and in vitro evaluation as potential anti-protozoal agent of (2E)-N-(1,3-benzothiazol-2-yl)-3-(2,5-dimethoxyphenyl)-2-propenamide (CAD-1) is presented. The results show that 0.05 mM CAD-1 induced 58.1% of T. cruzi epimastigotes death; mainly by apoptosis. The diminution in the transmembrane mitochondrial electrical potential together with the increase in the intracellular generation/accumulation of reactive oxygen species, suggest the parasites mitochondria as the main target for CAD-1-induced death. The concentration of 0.05 mM CAD-1 is not low enough to consider it as a potent tripanocydal agent. However the novel mechanism that induces T. cruzi death, together with the novelty of its chemical structure, point out CAD-1 as a head group compound that could serve as a template to obtain new, more potent anti-Chagas disease agents.

Key words

Anti-protozoal agents - Chagas’ disease - Cinnamic acid - Epimastigotes - Mitochondria - Oxidative stress - Trypanosoma cruzi
 

  • References

  • 1 Vinhaes MC, Schofield CJ. Trypanosomiasis control: surmounting diminishing returns. Trends Parasitol. 2003; 19: 112-113
    CrossrefPubMedSuche in Google Scholar
  • 2 Coura JR, De Castro SL. A critical review on Chagas disease chemotherapy. Mem Inst Oswaldo Cruz. 2002; 97: 3-24
    PubMedSuche in Google Scholar
  • 3 Castro JA, Montalto de Mecca M, Bartel LC. Toxic side effects of drugs used to treat Chagas’ disease (American trypanosomiasis). Hum Exp Toxicol. 2006; 25: 471-479
    CrossrefPubMedSuche in Google Scholar
  • 4 Halestrap AP. The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors. Biochem J. 1975; 148: 85-96
    PubMedSuche in Google Scholar
  • 5 Halestrap AP. Transport of pyruvate and lactate into human erythrocytes: evidence for the involvement of the chloride carrier and a chloride-independent carrier. Biochem J. 1976; 156: 193-207
    PubMedSuche in Google Scholar
  • 6 Pellón RF, Mamposo T, González E, Calderón O. Synthesis of cinnamic acid derivatives using ethanol as solvent or microwave assisted method. Synth Commun. 2000; 30: 3769-3774
    CrossrefPubMedSuche in Google Scholar
  • 7 Denicola-Seoane A, Rubbo H, Prodanov E, Turrens J. Succinate-dependent metabolism in Trypanosoma cruzi epimastigotes. Mol Biochem Parasit. 1992; 54: 43-50
    CrossrefPubMedSuche in Google Scholar
  • 8 Gornall AG, Bardawill CJ, David MM. Determination of serum proteins by means of biuret reaction. J Biol Chem. 1949; 177: 751-766
    PubMedSuche in Google Scholar
  • 9 Gomes A, Fernandes E, Lima JL. Fluorescence probes used for detection of reactive oxygen species. J Biochem Bioph Meth. 2005; 65: 45-80
    CrossrefPubMedSuche in Google Scholar
  • 10 Rottenberg H, Wu S. Quantitative assay by flow cytometry of the mitochondrial membrane potential in intact cells. Biochim Biophys Acta. 1998; 1404: 393-404
    CrossrefPubMedSuche in Google Scholar
  • 11 Buckner F, Yokoyama K, Lockman J, Aikenhead K, Ohkanda J, Sadilek M et al A class of sterol 14-demethylase inhibitors as anti-Trypanosoma cruzi agents. Proc Natl Acad Sci USA. 2003; 100: 15149-15153
    CrossrefPubMedSuche in Google Scholar
  • 12 Menna-Barreto RFS, Henriques-Pons A, Pinto AV, Morgado-Diaz JA, Soares MJ, De Castro SL. Effect of a b-lapachone-derived naphthoimidazole on Trypanosoma cruzi: identification of target organelles. J Antimicrob Chemoth. 2005; 56: 1034-1041
    CrossrefPubMedSuche in Google Scholar
  • 13 Piacenza L, Florencia I, Alvarez MN, Peluffo G, Taylor MC, Kelly JM et al Mitochondrial superoxide radicals mediate programmed cell death in Trypanosoma cruzi: cytoprotective action of mitochondrial iron superoxide dismutase overexpression. Biochem J. 2007; 403: 323-334
    CrossrefPubMedSuche in Google Scholar
  • 14 Viswalingam A, Caldwell J. Cinnamyl anthranilate causes coinduction of hepatic microsomal and peroxisomal enzymes in mouse but not rat. Toxicol Appl Pharmacol. 1997; 142: 338-347
    CrossrefPubMedSuche in Google Scholar