In Vitro Primary Screening of a Synthetic Series of Chromenoazoldiones against Trypanosoma cruzi ^†

Similarities between parasites and cancer have prompted parasitologists to take advantage of several approaches enabled by cancer research to identify antiparasitic agents [1]. Quinones generate reactive oxygen species (ROS), which not only results in their antitumor properties, but also in a mechanism for designing antichagasic drugs. Here, a synthetic series of seven chromenoazoldiones previously defined as potential antitumorals [2,3], has been assayed in vitro against Trypanosoma cruzi (CL-B5 lacZ strain) in a primary screening that evaluates activity over epimastigotes and toxicity on L929 cells [4,5]. Compounds PM199, PM203 and PM401 achieved higher IC₅₀ values than that of the reference drug benznidazole (BZ): IC₅₀ = 14.45 ± 1.90, 14.84 ± 4.49, 16.01 ± 9.06 and 36.47 ± 4.43 µM (PM199, PM203, PM401 and BZ, respectively). However, their higher cytotoxicity led to a lower selectivity (SI) on epimastigotes: SI_PM199 = 5.83, SI_PM203 = 7.03, SI_PM401 = 5.27 and SI_BZ > 7.02. Only two compounds showed no cytotoxicity (LC₅₀ > 256 µM) and thus, no derivative was further assayed against intracellular amastigotes. These chromenoazoldiones did not show relevant activity on T. cruzi. Their cytotoxicity, probably connected to ROS production in mammalian cells, encourages further optimization to apply them as trypanocidal templates.