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Trypanosoma cruzi: Inhibition of Parasite Growth and Respiration by Oxazolo(thiazolo)pyridine Derivatives and Its Relationship to Redox Potential and Lipophilicity

2001; Elsevier BV; Volume: 99; Issue: 1 Linguagem: Inglês

10.1006/expr.2001.4638

1090-2449

Juan Diego Maya, Antonio Morello, Yolanda Repetto, Andrés Rodrı́guez, Pilar Puebla, Esther Caballero, Manuel Medarde, Luis J. Núñez‐Vergara, J.A. Squella, María Eugenia Ortiz, Jorge Fuentealba, Arturo San Feliciano,

Synthesis and Biological Evaluation

Maya, J. D., Morello, A., Repetto, Y., Rodrı́guez, A., Puebla, P., Caballero, E., Medarde, M., Núñez-Vergara, L. J., Squella, J. A., Ortiz, M. E., Fuentealba, J., and San Feliciano, A. 2001. Trypanosoma cruzi: Inhibition of parasite growth and respiration by oxazolo(thiazolo)pyridine derivatives and its relationship to redox potential and lipophilicity. Experimental Parasitology99, 1–6. Chagas' disease constitutes a therapeutic challenge because presently available drugs have wide toxicity to the host and are generally ineffective in the chronic stages of the disease. A series of oxazolo(thiazolo)pyridene derivatives were studied on Trypanosoma cruzi epimastigote growth and oxygen consumption and their electrochemical (redox) potentials and lipophilicity. The derivatives produced different degrees of parasite growth and respiration inhibition on CL Brener, LQ, and Tulahuen strains of T. cruzi epimastigotes. Respiratory chain inhibition appears to be a determinant of the trypanosomicidal activity of these compounds, since a significant correlation between respiration and culture growth inhibition was found. A similar correlation was found, within the different structural subfamilies, between toxic effects and the ability of the compounds to be oxidized in aqueous media. The inhibition of respiration and of parasite growth in culture increases with the lipophilicity of the substituents on the oxazolopyridine nucleus. No difference in the action of these derivatives was found among the different parasite strains. It is concluded that these compounds may have a potential usefulness in the treatment of Chagas' disease.