Jacaranone Inspired Indole–Anisole Hybrids With Antiparasitic Activity

The search for new antiparasitic compounds against Trypanosoma cruzi , the causative agent of Chagas Disease, is still ongoing. The current treatments are highly toxic and not effective once the infection is established. Jacaranone is a natural quinone biosynthesized by plants of the Jacaranda genus, with reported cytotoxic and antiprotozoal activity. Inspired by its chemical structure and reactivity, 20 indole–anisole hybrids were synthesized and evaluated against intracellular amastigotes of Trypanosoma cruzi , the clinically relevant form of the parasite. Since the amastigotes replicate within the cytoplasm of the host‐cell, the cytotoxicity toward a human host‐cell line was also investigated. Two hits were found which displayed lower half maximal inhibitory concentrations than the reference drug as well as promising selectivity indexes.