Salgado, Francisco J.Moncada Basualto, MauricioPozo Martínez, JosuéLiempi, AnaKemmerling, UlrikeMaya, Juan DiegoJaque, PabloBorges, FernandaUriarte Villares, EugenioMatos, Maria João Correia Pinto Carvalho deOlea Azar, Claudio2021-02-052021-02-052021Arabian Journal of Chemistry, Volume 14, Issue 3, March 2021, 1029751878-5352http://hdl.handle.net/10347/24394Chagas disease is the most widespread contagious tropical disease in Latin America, being an important public health problem. Treatments against this disease are still very ineffective, presenting several side effects. Therefore, the search for alternative therapeutic solutions is urgent. In the present work, we evaluate the trypanocidal activity and the mechanism of action of a select series of synthetic 4-acyloxy-3-nitrocoumarins. All the coumarin derivatives showed moderate trypanocidal activity in trypomastigotes, along with low cytotoxicity. In addition, compound 1 decreased the number of infected Vero cells in an intracellular T. cruzi model. Electron spin resonance and electrochemical studies showed the formation of nitro radical anions. The Fukui index provided additional information to elucidate the proposed reduction mechanism. Furthermore, in vitro radical formation studies demonstrated the potential of these compounds to achieve higher concentrations of intracellular free radicals, proposing oxidative stress as a possible trypanocidal mechanism. Furthermore, no correlation was observed between the diffusion of these compounds, which shows that lipophilicity is not a predominant factor for activity. Elsevier Ltd. All rights reservedeng© 2020 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/NitrocoumarinsTrypanosoma cruziROSFukui indexjournal article10.1016/j.arabjc.2020.102975open access