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In Vitro and In Vivo Studies of the Trypanocidal Activity of Four Terpenoid Derivatives against Trypanosoma cruzi
Four terpenoid derivatives were examined for their activity against Trypanosoma cruzi. Our results show that two compounds were very active in vitro against both extra- and intracellular forms. These compounds, non-toxic for the host cells, are more effective than the reference drug benznidazole. The capacity to infect cells was negatively affected and the number of amastigotes and trypomastigotes was reduced. A wide range of ultrastructural alterations was found in the epimastigote forms treated with these compounds. Some metabolic changes occurred presumably at the level of succinate and acetate production, perhaps caused by the disturbance of the enzymes involved in sugar metabolism inside the mitochondria. In vivo results were consistent with those observed in vitro. The parasitic load was significantly lower than in the control assay with benznidazole. The effects of these products showed the reduction of the anti-T. cruzi antibodies level during the chronic stage.
Author Notes
Authors' addresses: Inmaculada Ramírez-Macías, Clotilde Marín, Francisco Olmo, María José Rosales, and Manuel Sánchez-Moreno, Department of Parasitology, University of Granada, Granada, Spain, E-mails: iramirezm@ugr.es, cmaris@ugr.es, folmoarevalo@ugr.es, mjrosale@ugr.es, and msanchem@ugr.es. Rachid Chahboun, Ibtissam Messouri, and Enrique Alvarez-Manzaneda, Department of Organic Chemistry, Institute of Biothenology, University of Granada, Granada, Spain. E-mails: spr@ugr.es, imessouri@yahoo.fr, and eamr@ugr.es. Ramòn Gutierrez-Sánchez, Department of Statistics, University of Granada, Granada, Spain, E-mail: ramongs@ugr.es.