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Anti-Trypanosoma cruzi and anti-leishmanial activity by quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives

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Abstract

In this work, a novel series of ethyl and methyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives were evaluated in vitro on Trypanosoma cruzi trypomastigotes and Leishmania mexicana promastigotes, and cytotoxicity activity in murine macrophages was tested. In silico molecular docking simulations of trypanothione reductase were also done. Three compounds of 33 quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives showed better anti-T. cruzi activity than nifurtimox and beznidazole; two compounds had better anti-leishmanial activity that amphotericin-B, and two compounds showed better activity against both parasites than reference drugs. Compounds M2, M7, M8 and E5, showed low cytotoxic activity on the host cell. The in silico studies suggest that compound M2 is a potential trypanothione reductase inhibitor.

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Acknowledgments

Juan Carlos Villalobos-Rocha is the recipient of a scholarship (228946) from CONACyT, Mexico. Benjamin Nogueda-Torres, Luvia Sánchez-Torres, Virgilio Bocanegra-García, and Gildardo Rivera hold a scholarship from the Comisión de Operación y Fomento de Actividades Académicas (COFAA-Instituto Politécnico Nacional) and the Programa de Estímulos al Desempeño de los Investigadores (EDI-Instituto Politécnico Nacional). Our gratitude to Lilia C. Gómez-Caro, Mario Sánchez-Sánchez, and Jesus Villegas-Mendoza for their support in this project. We wish to express our gratitude to the CONACyT (CB-2010-01, clave 0157358) and the Secretaria de Investigación y Posgrado of Instituto Politecnico Nacional (SIP-20130637 and SIP-20130768) for their financial support of this study.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Departamento de Parasitología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala, s/n, 11340, D.F., Mexico

    Juan Carlos Villalobos-Rocha & Benjamín Nogueda-Torres

  2. Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala, s/n, 11340, D.F., Mexico

    Luvia Sánchez-Torres

  3. Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Boulevard del Maestro, s/n, Esq. Elías Piña, 88710, Reynosa, Mexico

    Aldo Segura-Cabrera, Carlos A. García-Pérez, Virgilio Bocanegra-García & Gildardo Rivera

  4. Departamento de Química Aplicada, Universidad Autónoma de Tamaulipas, 88740, Reynosa, Mexico

    Isidro Palos

  5. Unidad de Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada, Universidad de Navarra, 31008, Pamplona, Spain

    Antonio Monge

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  1. Juan Carlos Villalobos-Rocha
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Correspondence to Gildardo Rivera.

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Villalobos-Rocha, J.C., Sánchez-Torres, L., Nogueda-Torres, B. et al. Anti-Trypanosoma cruzi and anti-leishmanial activity by quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives. Parasitol Res 113, 2027–2035 (2014). https://doi.org/10.1007/s00436-014-3850-8

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