Ligand-Based Virtual Screening and Molecular Docking of Benzimidazoles as Potential Inhibitors of Triosephosphate Isomerase Identified New Trypanocidal Agents

Authors

Lenci K. Vazquez-Jimenez, Instituto Politecnico Nacional, Mexico
Alfredo Juarez-Saldivar, Instituto Politecnico Nacional, Mexico
Rogelio Gomez-Escobedo
Timoteo Delgado-Maldonado
Domingo Mendez-Alvarez
Isidro Palos
Debasish Bandyopadhyay, The University of Texas Rio Grande ValleyFollow
Carlos Gaona-Lopez
Eyra Ortiz-Perez
Benjamin Nogueda-Torres
Esther Ramirez-Moreno
Gildardo Rivera

Document Type

Article

Publication Date

9-17-2022

Abstract

Trypanosoma cruzi (T. cruzi) is a parasite that affects humans and other mammals. T. cruzi depends on glycolysis as a source of adenosine triphosphate (ATP) supply, and triosephosphate isomerase (TIM) plays a key role in this metabolic pathway. This enzyme is an attractive target for the design of new trypanocidal drugs. In this study, a ligand-based virtual screening (LBVS) from the ZINC15 database using benzimidazole as a scaffold was accomplished. Later, a molecular docking on the interface of T. cruzi TIM (TcTIM) was performed and the compounds were grouped by interaction profiles. Subsequently, a selection of compounds was made based on cost and availability for in vitro evaluation against blood trypomastigotes. Finally, the compounds were analyzed by molecular dynamics simulation, and physicochemical and pharmacokinetic properties were determined using SwissADME software. A total of 1604 molecules were obtained as potential TcTIM inhibitors. BP2 and BP5 showed trypanocidal activity with half-maximal lytic concentration (LC₅₀) values of 155.86 and 226.30 µM, respectively. Molecular docking and molecular dynamics simulation analyzes showed a favorable docking score of BP5 compound on TcTIM. Additionally, BP5 showed a low docking score (−5.9 Kcal/mol) on human TIM compared to the control ligand (−7.2 Kcal/mol). Both compounds BP2 and BP5 showed good physicochemical and pharmacokinetic properties as new anti-T. cruzi agents. View Full-Text

Comments

Copyright the Authors.

Recommended Citation

Vázquez-Jiménez LK, Juárez-Saldivar A, Gómez-Escobedo R, Delgado-Maldonado T, Méndez-Álvarez D, Palos I, Bandyopadhyay D, Gaona-Lopez C, Ortiz-Pérez E, Nogueda-Torres B, Ramírez-Moreno E, Rivera G. Ligand-Based Virtual Screening and Molecular Docking of Benzimidazoles as Potential Inhibitors of Triosephosphate Isomerase Identified New Trypanocidal Agents. International Journal of Molecular Sciences. 2022; 23(17):10047. https://doi.org/10.3390/ijms231710047

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Title

International Journal of Molecular Sciences

DOI

10.3390/ijms231710047