Title:Structure-Based Virtual Screening of New Benzoic Acid Derivatives as Trypanosoma cruzi Trans-sialidase Inhibitors
Volume: 17
Issue: 7
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*
Affiliation:
- Laboratorio de Biotecnologia Farmaceutica, Centro de Biotecnologia Genomica, Instituto Politecnico Nacional, 88710, Reynosa,Mexico
Keywords:
Virtual screening, molecular docking, trans-sialidase, Trypanosoma cruzi, trypanocidal activity, enzymatic inhibition.
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.