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Synthesis and biological evaluation in vitro and in silico of N-propionyl-N′-benzeneacylhydrazone derivatives as cruzain inhibitors of Trypanosoma cruzi

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Abstract

An N-acylhydrazone scaffold has been used to develop new drugs with diverse biological activities, including trypanocidal activity against different strains of Trypanosoma cruzi. However, their mechanism of action is not clear, although in T. cruzi it has been suggested that the enzyme cruzain is involved. The aim in this work was to obtain new N-propionyl-N′-benzeneacylhydrazone derivatives as potential anti-T. cruzi agents and elucidate their potential mechanism of action by a molecular docking analysis and effects on the expression of the cruzain gene. Compounds 9 and 12 were the most active agents against epimastigotes and compound 5 showed better activity than benznidazole in T. cruzi blood trypomastigotes. Additionally, compounds 9 and 12 significantly increase the expression of the cruzain gene. In summary, the in silico and in vitro data presented herein suggest that compound 9 is a cruzain inhibitor.

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Acknowledgements

This research was funded by Secretaria de Investigacion y Posgrado del Instituto Politecnico Nacional (SIP-20200491). Gildardo Rivera Sánchez and Benjamin Nogueda-Torres holds a scholarship from the “Comisión de Operación y Fomento de Actividades Académicas” (COFAA-IPN) and “Programa de Estímulos al Desempeño de los Investigadores” (EDI-IPN). José Carlos Espinoza-Hicks is thankful to the Consejo Nacional de Ciencia y Tecnología (CONACYT,Mexico) for a grant to purchase the NMR instrument (INFR-2014-01-226114).

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Authors and Affiliations

  1. Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710, Reynosa, Mexico

    Timoteo Delgado-Maldonado, Lenci K. Vázquez-Jiménez, Alma D. Paz-González, Alfredo Juárez-Saldívar & Gildardo Rivera

  2. Departamento de Parasitología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, 11340, Ciudad de México, Mexico

    Benjamín Nogueda-Torres

  3. Laboratorio de Química II, Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Circuito Universitario, Campus Universitario, Apartado Postal 669, Chihuahua, Chih., Mexico

    José C. Espinoza-Hicks

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Delgado-Maldonado, T., Nogueda-Torres, B., Espinoza-Hicks, J.C. et al. Synthesis and biological evaluation in vitro and in silico of N-propionyl-N′-benzeneacylhydrazone derivatives as cruzain inhibitors of Trypanosoma cruzi. Mol Divers 26, 39–50 (2022). https://doi.org/10.1007/s11030-020-10156-5

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