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Structure-Based Virtual Screening of New Benzoic Acid Derivatives as Trypanosoma cruzi Trans-sialidase Inhibitors

Author(s):

Lenci Karina Vázquez-Jiménez, Alma Delia Paz-González, Alfredo Juárez-Saldivar, María Laura Uhrig, Rosalía Agusti, Alicia Reyes-Arellano, Benjamín Nogueda-Torres and Gildardo Rivera*   Pages 1 - 8 ( 8 )

Abstract:


Background: Chagas disease, caused by the parasite Trypanosoma cruzi represents a worldwide epidemiological, economic, and social problem. In the last decades, the trans-sialidase enzyme of Trypanosoma cruzi has been considered an attractive target for the development of new agents with potential trypanocidal activity.

Objective: In this work, the aim was find new potential non-sugar trans-sialidase inhibitors using benzoic acid as a scaffold.

Method: A structure-based virtual screening of the ZINC15 database was carried out. Additionally, the enzyme and trypanocidal activity of the selected compounds was determined.

Results: The results of this work detected 487 compounds derived from benzoic acid as potential trans-sialidase inhibitors with a more promising binding energy value (< -7.7 kcal/mol) than the known inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). In particular, two lead compounds, V1 and V2 turned out to be promising trans-sialidase inhibitors. Even though the trypanocidal activity displayed was low, these compounds showed trans-sialidase inhibition values of 87.6% and 29.6%, respectively.

Conclusion: Structure-based virtual screening using a molecular docking approach is a useful method for the identification of new transsialidase inhibitors.

Keywords:

Virtual screening, molecular docking, trans-sialidase, Trypanosoma cruzi, trypanocidal activity, enzymatic inhibition.

Affiliation:

Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710, Reynosa, Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710, Reynosa, Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710, Reynosa, Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Orgánica, Buenos Aires, Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Orgánica, Buenos Aires, Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, 11340, Ciudad de México, Departamento de Parasitología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, 11340, Ciudad de México, Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710, Reynosa



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