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American trypanosomiasis (Chagas disease) caused by the Trypanosoma cruzi parasite, is a severe health problem in different regions of Latin America and is currently reported to be spreading to Europe, North America, Japan, and Australia, due to the migration of populations from South and Central America. At present, there is no vaccine available and chemotherapeutic options are reduced to nifurtimox and benznidazole. Therefore, the discovery of new molecules is urgently needed to initiate the drug development process. Some acetophenones and chalcones, as well as chromane-type substances, such as chromones and flavones, are natural products that have been studied as trypanocides, but the relationships between structure and activity are not yet fully understood. In this work, 26 compounds were synthesized to determine the effect of hydroxyl and isoprenyl substituents on trypanocide activity. One of the compounds showed interesting activity against a resistant strain of T. cruzi , with a half effective concentration of 18.3 µM ± 1.1 and an index of selectivity > 10.9.

Six derivatives of the known biopesticide rotenone were prepared by several chemical transformations. Rotenone and its derivatives showed differential in vitro antiparasitic activity and selective cytotoxicity. In general, compounds were more active against Plasmodium falciparum than Leishmania panamensis. Rotenone had an EC50 of 19.0 µM against P. falciparum, and 127.2 µM against L. panamensis. Although chemical transformation does not improve its biological profile against P. falciparum, three of its derivatives showed a significant level of action within an adequate range of activity with EC50 values < 50.0 µM. This antiplasmodial activity was not due to red blood cell hemolysis, since LC50 was >>400 µM. On the other hand, all derivatives displayed a non-specific cytotoxicity on several cell lines and primary human cell cultures.