Medicinal Chemistry Research

, Volume 22, Issue 6, pp 2768–2777 | Cite as

Synthesis and theoretic calculations of benzoxazoles and docking studies of their interactions with triosephosphate isomerase

  • César A. Flores Sandoval
  • Roberto I. Cuevas Hernández
  • José Correa Basurto
  • Hiram I. Beltrán Conde
  • Itzia I. Padilla Martínez
  • José N. Farfán García
  • Benjamín Nogueda Torres
  • José G. Trujillo Ferrara
Original Research


One-pot synthesis was carried out for Z or E stereoisomer derivates of 3-(benzoxazoyl)-2-propenoic acid following kinetic or thermodynamic control. All compounds were characterized by 1H and 13C NMR, and the single crystal X-ray structure of (2Z)-3-(6-methyl-1,3-benzoxazol-2-yl)prop-2-enoic acid (3) was obtained. Furthermore, a theoretic study was done for all the synthesized compounds at the B3LYP/6-31G(d,p) level. The target compounds were docked on triosephosphate isomerase and trypanocidal activity was explored for the 4 and 6 compounds. The Z isomers showed an intramolecular hydrogen bond O–H···N according to the X-ray structure of 3. The docking studies indicate that the test compounds insert themselves between the monomers of triosephosphate isomerase, reaching the known binding site located at interdimeric shapes of triosephosphate isomerase by means of π–π interactions and electrostatic interactions, and in this way interrupt interactions between these monomers. Thus, could explain the biologic effects of the E isomer on triosephosphate isomerase. Finally, compounds 4 and 6 showed trypanocidal activity, which could be mediated by triosephosphate isomerase inhibition.


Stereoisomers Molecular modeling Molecular docking Triosephophate isomerase 



We thank “Proyecto D.00343 del Instituto Mexicano del Petróleo,” “Competencia de Química Aplicada del Instituto Mexicano del Petróleo,” Consejo Nacional de Ciencia y Tecnología (CONACyT), Comisión de Operación y Fomento de Actividades Académicas del Instituto Politécnico Nacional (COFAA-IPN), and Instituto de Ciencia y Tecnología del Distrito Federal (ICyTDF) for financial support.

Supplementary material

44_2012_264_MOESM1_ESM.docx (366 kb)
Supplementary material 1 (DOCX 366 kb)


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • César A. Flores Sandoval
    • 1
  • Roberto I. Cuevas Hernández
    • 2
  • José Correa Basurto
    • 2
  • Hiram I. Beltrán Conde
    • 3
  • Itzia I. Padilla Martínez
    • 4
  • José N. Farfán García
    • 5
  • Benjamín Nogueda Torres
    • 6
  • José G. Trujillo Ferrara
    • 2
  1. 1.Programa de ingeniería MolecularInstituto Mexicano del PetróleoMexicoMexico
  2. 2.Laboratorio de Modelado Molecular y Bioinformática, Departamento de Bioquímica, Escuela Superior de MedicinaInstituto Politécnico NacionalMexicoMexico
  3. 3.Departamento de Ciencias NaturalesUAM-CuajimalpaMexicoMexico
  4. 4.Unidad Profesional Interdisciplinaria de BiotecnologíaInstituto Politécnico NacionalMexicoMexico
  5. 5.Departamento de Química, Facultad de QuímicaUNAM, Ciudad UniversitariaMexicoMexico
  6. 6.Departamento de ParasitologíaEscuela Nacional de Ciencias Biológicas, Instituto Politécnico NacionalMexicoMexico

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