Chemical and biological analysis of 4-acyloxy-3-nitrocoumarins as trypanocidal agents
| Autor: | Maria João Matos, Claudio Olea-Azar, Josué Pozo-Martínez, Mauricio Moncada-Basualto, Ana Liempi, Ulrike Kemmerling, Pablo Jaque, Fernanda Borges, Juan-Diego Maya, Eugenio Uriarte, Francisco Salas Salgado |
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| Přispěvatelé: | Universidade de Santiago de Compostela. Departamento de Química Orgánica |
| Rok vydání: | 2021 |
| Předmět: |
Fukui index
Chemistry General Chemical Engineering Trypanosoma cruzi Library science ROS 02 engineering and technology General Chemistry 010402 general chemistry 021001 nanoscience & nanotechnology 01 natural sciences language.human_language 0104 chemical sciences lcsh:Chemistry lcsh:QD1-999 language Portuguese 0210 nano-technology Nitrocoumarins Trypanocidal agent |
| Zdroj: | Minerva: Repositorio Institucional de la Universidad de Santiago de Compostela Universidad de Santiago de Compostela (USC) Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela instname Arabian Journal of Chemistry, Vol 14, Iss 3, Pp 102975-(2021) |
| Popis: | Chagas 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 reserved This project was partially supported by the University of Porto and University of Santiago de Compostela. MJM would like to thank Xunta de Galicia (Galician Plan of Research, Innovation and Growth 2011–2015, Plan I2C, ED481B 2014/086–0 and ED481B 2018/007) and Fundação para a Ciência e Tecnologia (CEECIND/02423/2018 and UIDB/00081/2020). FS would like to thank FONDECYT 1190340 and REDES170126, COA would like to thank FONDECYT 1190340, JDM would like to thank FONDECYT 1170126 and ANID/PCI REDES 170126, and MMB would like to thank FONDECYT Postdoctoral 3190449 SI |
| Databáze: | OpenAIRE |
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