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: SIPM199 = 5.83, SIPM203 = 7.03, SIPM401 = 5.27 and SIBZ > 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.
Author Contributions
P.M. and N.J. have designed and synthesized the compounds studied in the present work. C.F.-B., J.A.E. and A.G.-B. have conceived and designed the biological experiments for testing the activity of compounds. C.F.-B. has performed the trypanocidal and cytotoxicity assays in vitro. All authors have contributed to write this abstract. All authors have read and agreed to the published version of the manuscript.
Acknowledgments
The authors thank the Spanish Ministry of Economy, Industry and Competitiveness (MINEICO, ref. SAF2015-66690-R and ref. SAF2015-68580-C2-2-R), the PICATA Program of CEI Campus Moncloa (UCM-UPM & CSIC) and the 911120 UCM-CEI Moncloa Research Group.
Conflicts of Interest
The authors declare no conflict of interest.
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