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Medicinal Chemistry

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*

DOI: 10.2174/1573406416666200506084611

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

Page: [724 - 731] Pages: 8

  • * (Excluding Mailing and Handling)

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 to find new potential non-sugar trans-sialidase inhibitors using benzoic acid as a scaffold.

Methods: 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 transsialidase 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 trans-sialidase inhibitors.

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

Graphical Abstract

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