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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.

Abstract

Chagas disease is responsible for a large number of human infections and many are also at risk of infection. There is no effective drug for Chagas disease treatment. The Institute of Pharmaceutical Technology at Fiocruz, Brazil, has designed three nitro analogs of the nitroimidazole-thiadiazole, megazol: two triazole analogs PTAL 05-02 and PAMT 09 and a pyrazole analog PTAL 04-09. A set of Salmonella enterica serovar Typhimurium strains were used in the bacterial reverse mutation test (Ames test) to determine the mutagenicity and cytotoxicity of megazol and its nitro analogs. Megazol presented positive mutagenic activity at very low concentration, either with or without metabolic activation S9 mix. The mutagenic response of the analogs was detected at higher concentration than the lowest megazol concentration to yield mutagenic activity showing that new advances can be made to develop new analogs. The micronucleus test with rat macrophage cells was used in the genotoxic evaluation. The analogs were capable of inducing micronucleus formation and showed cytotoxic effects. PTAL 04-09 structural modifications might be better suitable for the design of promising new drugs candidate for Chagas’ disease treatment.