Table of Contents Author Guidelines Submit a Manuscript
The Scientific World Journal
Volume 2013 (2013), Article ID 287319, 8 pages
http://dx.doi.org/10.1155/2013/287319
Research Article

Evaluation of Genotoxic Effects of New Molecules with Possible Trypanocidal Activity for Chagas Disease Treatment

1Department of Biophysics and Biometry, Rio de Janeiro State University, Boulevard 28 de Setembro, 87 Fundos, 4º Andar, 20551-030 Rio de Janeiro, RJ, Brazil
2Institute of Pharmaceutical Technology, Oswaldo Cruz Institute, Rua Sizenando Nabuco 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil
3Department of Genetics and Molecular Biology, Federal University of the State of Rio de Janeiro, Rua Frei Caneca, 95 Centro, 20211-040 Rio de Janeiro, RJ, Brazil

Received 12 August 2013; Accepted 19 September 2013

Academic Editors: S. S. Anand, C. Garcia, and L. Schnackenberg

Copyright © 2013 Francisco V. C. Mello et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. World Health Organization, Working to Overcome the Global Impact of Neglected Tropical Diseases, 2010.
  2. J. R. Cançado, “Tratamento específico,” in Cardiopatia Chagásica, J. R. Cançado and M. Chuster, Eds., pp. 327–355, Imprensa Oficial de Minas Gerais, Minas Gerais, Brazil, 1985. View at Google Scholar
  3. H. O. Ferreira, “Tratamento da forma indeterminada da Doença de Chagas com nifurtimox e benznidazol,” Revista da Sociedade Brasileira de Medicina Tropical, vol. 23, no. 4, pp. 209–211, 1990. View at Google Scholar
  4. A. Buschini, F. Giordani, C. N. de Albuquerque et al., “Trypanocidal nitroimidazole derivatives: relationships among chemical structure and genotoxic activity,” Biochemical Pharmacology, vol. 73, no. 10, pp. 1537–1547, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. J. A. Castro, “Contributions of toxicology to the problem of chagas' disease (american trypanosomiasis)—a year 2000 update,” Biomedical and Environmental Sciences, vol. 13, no. 4, pp. 271–279, 2000. View at Google Scholar · View at Scopus
  6. G. Berkelhammer and G. Asato, “2-Amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole: a new antimicrobial agent,” Science, vol. 162, no. 3858, pp. 1146–1148, 1968. View at Google Scholar · View at Scopus
  7. L. S. Filardi and Z. Brener, “A nitroimidazole-thiadiazole derivative with curative action in experimental Trypanosoma cruzi infections,” Annals of Tropical Medicine and Parasitology, vol. 76, no. 3, pp. 293–297, 1982. View at Google Scholar · View at Scopus
  8. C. N. Albuquerque and J. J. Perie, “Nova rota de síntese do megazol. [1-metil-2-(5-amino-1, 3, 4-tiadiazol-2-il)-5-nitroimidazol], fármaco antichagásico,” Revista Brasileira de Ciência e Farmacologia, vol. 35, pp. 57–64, 1999. View at Google Scholar
  9. G. Chauvière, B. Bouteille, B. Enanga et al., “Synthesis and biological activity of nitro heterocycles analogous to megazol, a trypanocidal lead,” Journal of Medicinal Chemistry, vol. 46, no. 3, pp. 427–440, 2003. View at Publisher · View at Google Scholar · View at Scopus
  10. S. L. de Castro and M. N. Meirelles, “Mechanism of action of a nitroimidazole-thiadiazole derivate upon Trypanosoma cruzi tissue culture amastigotes,” Memorias do Instituto Oswaldo Cruz, vol. 85, no. 1, pp. 95–99, 1990. View at Google Scholar · View at Scopus
  11. M. P. Barrett, A. H. Fairlamb, B. Rousseau, G. Chauvière, and J. Perié, “Uptake of the nitroimidazole drug megazol by African trypanosomes,” Biochemical Pharmacology, vol. 59, no. 6, pp. 615–620, 2000. View at Publisher · View at Google Scholar · View at Scopus
  12. C. É. Viodé, N. Bettache, N. Cenas et al., “Enzymatic reduction studies of nitroheterocycles,” Biochemical Pharmacology, vol. 57, no. 5, pp. 549–557, 1999. View at Publisher · View at Google Scholar · View at Scopus
  13. B. Enanga, M. R. Ariyanayagam, M. L. Stewart, and M. P. Barrett, “Activity of megazol, a trypanocidal nitroimidazole, is associated with DNA damage,” Antimicrobial Agents and Chemotherapy, vol. 47, no. 10, pp. 3368–3370, 2003. View at Publisher · View at Google Scholar · View at Scopus
  14. F. Nesslany, S. Brugier, M.-A. Mouriès, F. Le Curieux, and D. Marzin, “In vitro and in vivo chromosomal aberrations induced by megazol,” Mutation Research, vol. 560, no. 2, pp. 147–158, 2004. View at Publisher · View at Google Scholar · View at Scopus
  15. A. S. Carvalho, R. F. S. Menna-Barreto, N. C. Romeiro, S. L. de Castro, and N. Boechat, “Design, synthesis and activity against Trypanosoma cruzi azaheterocyclic analogs of megazol,” Medicinal Chemistry, vol. 3, no. 5, pp. 460–465, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. N. Boechat, A. S. Carvalho, E. Fernandez-Ferreira et al., “Novel nitroimidazoles with trypanocidal and cell growth inhibition activities,” Cytobios, vol. 2001, no. 409, pp. 83–90, 2001. View at Google Scholar · View at Scopus
  17. World Health Organization, New Global Effort to Eliminate Chagas Disease, Partners Set Out Strategy Against the “Kissing Bug” Disease, 2007.
  18. D. M. Maron and B. N. Ames, “Revised methods for the Salmonella mutagenicity test,” Mutation Research, vol. 113, no. 3-4, pp. 173–215, 1983. View at Google Scholar · View at Scopus
  19. K. Mortelmans and E. Zeiger, “The Ames Salmonella/microsome mutagenicity assay,” Mutation Research, vol. 455, no. 1-2, pp. 29–60, 2000. View at Publisher · View at Google Scholar · View at Scopus
  20. OECD, “OECD guideline for testing of chemicals: bacterial reverse mutation test,” 1997, http://www.oecd-ilibrary.org/environment/test-no-471-bacterial-reverse-mutation-test_9789264071247-en.
  21. P. M. Eckl, W. R. Whitcomb, G. Michalopoulos, and R. L. Jirtle, “Effects of EGF and calcium on adult parenchymal hepatocyte proliferation,” Journal of Cellular Physiology, vol. 132, no. 2, pp. 363–366, 1987. View at Google Scholar · View at Scopus
  22. OECD, “OECD guideline for the testing of chemicals: In Vitro Mammalian Cell Micronucleus Test,” 2010, http://www.oecd-ilibrary.org/environment/test-no-487-in-vitro-mammalian-cell-micronucleus-test_9789264091016-en.
  23. L. D. Claxton, J. Allen, A. Auletta, K. Mortelmans, E. Nestmann, and E. Zeiger, “Guide for the Salmonella typhimurium/mammalian microsome tests for bacterial mutagenicity,” Mutation Research, vol. 189, no. 2, pp. 83–91, 1987. View at Google Scholar · View at Scopus
  24. R. C. C. Ferreira and L. C. S. Ferreira, “Mutagenicity of CL 64855, a potent anti-Trypanosoma cruzi drug,” Mutation Research, vol. 171, no. 1, pp. 11–15, 1986. View at Google Scholar · View at Scopus
  25. R. C. Ferreira and L. C. Ferreira, “CL 64,855, a potent anti-Trypanosoma cruzi drug, is also mutagenic in the Salmonella/microsome assay,” Memorias do Instituto Oswaldo Cruz, vol. 81, no. 1, pp. 49–52, 1986. View at Google Scholar · View at Scopus
  26. M. A. De Morais Jr., R. C. C. De Ferreira, and L. C. S. De Ferreira, “Mutagenic activation of CL64,855, an anti-Trypanosoma cruzi nitroderivant, by bacterial nitroreductases,” Genetics and Molecular Biology, vol. 21, no. 4, pp. 567–572, 1998. View at Google Scholar · View at Scopus
  27. J. Molina, O. Martins-Filho, Z. Brener, A. J. Romanha, D. Loebenberg, and J. A. Urbina, “Activities of the triazole derivative SCH 56592 (Posaconazole) against drug-resistant strains of the protozoan parasite Trypanosoma (Schizotrypanum) cruzi in immunocompetent and immunosuppressed murine hosts,” Antimicrobial Agents and Chemotherapy, vol. 44, no. 1, pp. 150–155, 2000. View at Google Scholar · View at Scopus
  28. H. Cerecetto and M. González, “Chemotherapy of Chagas' disease: status and new developments,” Current Topics in Medicinal Chemistry, vol. 2, no. 11, pp. 1187–1213, 2002. View at Google Scholar · View at Scopus
  29. J. A. Urbina, G. Payares, C. Sanoja et al., “Parasitological cure of acute and chronic experimental Chagas disease using the long-acting experimental triazole TAK-187. Activity against drug-resistant Trypanosoma cruzi strains,” International Journal of Antimicrobial Agents, vol. 21, no. 1, pp. 39–48, 2003. View at Publisher · View at Google Scholar · View at Scopus
  30. V. G. Duschak and A. S. Couto, “An insight on targets and patented drugs for chemotherapy of chagas disease,” Recent Patents on Anti-Infective Drug Discovery, vol. 2, no. 1, pp. 19–51, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. J. S. Walsh, R. Wang, E. Bagan, C. C. Wang, P. Wislocki, and G. T. Miwa, “Structural alterations that differentially affect the mutagenic and antitrichomonal activities of 5-nitroimidazoles,” Journal of Medicinal Chemistry, vol. 30, no. 1, pp. 150–156, 1987. View at Google Scholar · View at Scopus