Esters of Quinoxaline-7-Carboxylate 1,4-di-N-Oxide as Potential Inhibitors
of Glycolytic Enzymes of Entamoeba histolytica: In silico Approach

Jacqueline      Soto-Sánchez; Salvador      Pérez-Mora; Juan   David   Ospina-Villa; Lizeth   Mariel   Zavala-Ocampo
doi:10.2174/1573409919666230417135204
Abstract

Background: Esters of quinoxaline-7-carboxylate 1,4-di-N-oxide (7-carboxylate QdNOs) derivatives are compounds that inhibit the growth of Entamoeba histolytica, the causative agent of amebiasis. Although these compounds cause changes in the redistribution of glycogen deposits within the parasite, it is unknown whether these compounds interact with enzymes of the glycolytic pathway.
Objective: The aim of this study was to test the binding affinity of these compounds to pyrophosphate- dependent phosphofructokinase (PPi-PFK), triosephosphate isomerase (TIM), and pyruvate phosphate dikinase (PPDK) from E. histolytica as a possible mechanism of action.
Methods: The molecular docking study of the 7-carboxylate QdNOs derivatives and the proteins was performed using AutoDock/Vina software. Molecular dynamics simulation was performed for 100 ns.
Results: Among all the selected compounds, T-072 exhibited the best binding affinity to EhPPi- PFK and EhTIM proteins, while T-006 interacted best with EhPPDK. ADMET analysis revealed that T-072 was non-toxic, while T-006 could become harmful to the host. In addition, molecular dynamics showed that T-072 has stable interaction with EhPPi-PFK and EhTIM.
Conclusion: Including all aspects, these data indicated that these compounds might inhibit the activity of key enzymes in energy metabolism leading to parasite death. Furthermore, these compounds may be a good starting point for the future development of new potent antiamebic agents.
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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1573409919666230417135204	Print ISSN 1573-4099
Publisher Name Bentham Science Publisher	Online ISSN 1875-6697
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Esters of Quinoxaline-7-Carboxylate 1,4-di-N-Oxide as Potential Inhibitors of Glycolytic Enzymes of Entamoeba histolytica: In silico Approach

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