Medicinal Chemistry Research

, Volume 27, Issue 6, pp 1705–1716 | Cite as

Structural characterization, biochemical, inhibition and computational studies of Entamoeba histolytica phosphoglycerate mutase: finding hits for a new antiamoebic drug

  • Artemisa Luévano-De la Cruz
  • Elkin Eduardo Sanabria-Chanaga
  • Lilián Yépez-Mulia
  • Rafael Castillo
  • Alicia Hernández-Campos
  • Hugo Nájera
  • Claudia Avitia-Domínguez
  • Erick Sierra-Campos
  • Mónica Valdez-Solana
  • Alfredo Téllez-Valencia
Original Research


Entamoeba histolytica is the causative agent of amoebiasis, which infects an estimated 50 million people globally each year. This parasite uses glycolysis as its only source of energy making enzymes of this route such as phosphoglycerate mutase (EhPGAM) excellent targets in the search for new drugs, a continuing necessity due to the adverse effects and unsuccessful cases of treatment that have resulted from the use of available antiparasitic agents. The aim of this work is to present the biochemical and structural characterization of EhPGAM and the results of a search for the first inhibitors of this enzyme. To this end, the activity of purified recombinant EhPGAM was assessed against an in-house chemical library of 200 benzimidazole derivatives. The results showed that seven compounds inhibited this enzyme about 40–70% at 100 μM and molecular dynamics simulations indicated that the two most potent inhibitors (Compound 1 and Compound 2) form stable complexes and have the highest binding energy. Hence, these inhibitors can be considered good candidates in the search of new drugs to treat amoebiasis.


Amoebiasis Phosphoglycerate mutase Enzyme inhibition Homology modeling Molecular dynamics Benzimidazole derivatives 



The authors acknowledge DGESCA for the use of supercomputer Miztli. ATV and CAD acknowledge CONACyT for grants No. 257848 and No. 258694, respectively. CONACyT is also acknowledged by ALC (fellowship No. 231153) and EESC (fellowship No. 283595).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Artemisa Luévano-De la Cruz
    • 1
  • Elkin Eduardo Sanabria-Chanaga
    • 2
  • Lilián Yépez-Mulia
    • 3
  • Rafael Castillo
    • 2
  • Alicia Hernández-Campos
    • 2
  • Hugo Nájera
    • 4
  • Claudia Avitia-Domínguez
    • 1
  • Erick Sierra-Campos
    • 5
  • Mónica Valdez-Solana
    • 5
  • Alfredo Téllez-Valencia
    • 1
  1. 1.Facultad de Medicina y NutriciónUniversidad Juárez del Estado de Durango Av. Universidad y Fanny Anitúa S/NDurangoMexico
  2. 2.Facultad de Química, Departamento de FarmaciaUniversidad Nacional Autónoma de MéxicoCiudad de MéxicoMexico
  3. 3.IMSSUnidad de Investigación Médica en Enfermedades Infecciosas y ParasitariasCiudad de MéxicoMexico
  4. 4.Departamento de Ciencias NaturalesUniversidad Autónoma Metropolitana, Unidad Cuajimalpa Av. Vasco de Quiroga 4871, Colonia Santa Fe Cuajimalpa, Delegación Cuajimalpa de MorelosCiudad de MéxicoMexico
  5. 5.Facultad de Ciencias QuímicasUniversidad Juárez del Estado de DurangoDurangoMexico

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