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

Abstract

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.

Keywords

Stereoisomers Molecular modeling Molecular docking Triosephophate isomerase 

Notes

Acknowledgments

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)

References

  1. Arnold C Jr (1979) Stability of high-temperature polymers. J Polym Sci Macromol Rev 14:265–378CrossRefGoogle Scholar
  2. Bader RFW (1990) Atoms in molecules: a quantum theory. Oxford University Press, OxfordGoogle Scholar
  3. Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652CrossRefGoogle Scholar
  4. Beebe X et al (2001) Solid-phase synthesis of benzoxazoles from 3-nitrotyrosine. J Comb Chem 3:360–366PubMedCrossRefGoogle Scholar
  5. Bolelli K et al. (2011) Synthesis of novel 2-[4-(4-substitutedbenzamido/phenylacetamido)phenyl]benzothiazoles as antimicrobial agents. Med Chem Res. doi: 10.1007/s00044-011-9918-4
  6. Boyd GV (1984) Comprehensive Heterocyclic Chemistry. Pergamon Press, OxfordGoogle Scholar
  7. Bunnet JF, Hrutfiord BF (1961) Ring closure via aryne intermediates: a general principle of synthesis. J Am Chem Soc 83:1691–1697CrossRefGoogle Scholar
  8. Caputo R et al (2011) Synthesis of benzothiazole derivatives and their biological evaluation as anticancer agents. Med Chem Res 21:2644–2651CrossRefGoogle Scholar
  9. Carpenter JE, Weirnhol F (1988) Analysis of the geometry of the hydroxymethyl radical by the “different hybrids for different spins” natural bond orbital procedure. J Mol Struct 169:41–62CrossRefGoogle Scholar
  10. Cassidy PE (1980) Thermally stable polymers, synthesis and properties. Marcel Dekker, New YorkGoogle Scholar
  11. Chen Y, Zeng DX (2004) Study on photochromic diarylethene with phenolic Schiff base: preparation and photochromism of diarylethene with benzoxazole. J Org Chem 69:5037–5040PubMedCrossRefGoogle Scholar
  12. Choe EW, Kim SN (1981) Synthesis, spinning, and fiber mechanical properties of poly(p-phenylenebenzobisoxazole). Macromolecules 14:920–924CrossRefGoogle Scholar
  13. Chow AW et al (1989) Synthesis and solution properties of extended chain poly(2,6-benzothiazole) and poly(2,5-benzoxazole). Macromolecules 22:3514–3520CrossRefGoogle Scholar
  14. Clark RD, Caroon JM (1982) Preparation and electrophilic trapping of 7-lithiated benzoxazoles generated via benzyne cyclization. J Org Chem 47:2804–2806CrossRefGoogle Scholar
  15. Díaz DL et al (2011) In vitro and in vivo trypanocidal activity of some benzimidazole derivatives against two strains of Trypanosoma cruzi. Acta Trop. doi: 10.1016/j.actatropica.2011.12.009 Google Scholar
  16. El-Sheikh MI, Marks A, Biehl ER (1981) Investigation of the synthesis of benzoxazole via aryne reaction. J Org Chem 46:3256–3259CrossRefGoogle Scholar
  17. Espinoza LM, Trujillo JG (2005) Structural considerations for the rational design of selective anti-trypanosomal agents: the role of the aromatic clusters at the interface of triosephosphate isomerase dimer. Biochem Biophys Res Commun 25(328):922–928CrossRefGoogle Scholar
  18. Espinoza LM, Trujillo JG (2006) Toward a rational design of selective multi-trypanosomatid inhibitors: a computational docking study. Bioorg Med Chem Lett 16:6288–6292CrossRefGoogle Scholar
  19. Espinoza LM et al (2010) Tyr74 is essential for the formation, stability and function of Plasmodium falciparum triosephosphate isomerase dimer. Arch Bio chem Biophys 494(1):46–57CrossRefGoogle Scholar
  20. Foster JP, Weinhold F (1980) Natural hybrid orbitals. J Am Chem Soc 102:7211–7218CrossRefGoogle Scholar
  21. Frisch MJ et al (1998) Gaussian 98, Revision A.9. Gaussian Inc, PittsburghGoogle Scholar
  22. Fukukawa K et al (2004) A photosensitive semi-alicyclic poly(benzoxazole) with high transparency and low dielectric constant. Macromolecules 37:8256–8261CrossRefGoogle Scholar
  23. Hernández JV et al (2003) Enantioselective chromenone benzoxazole receptor for glutamic acid and its derivatives. J Org Chem 68:7513–7516PubMedCrossRefGoogle Scholar
  24. Humphrey W et al (1996) VMD: visual molecular dynamics. J Mol Graph 14(33–8):27–28Google Scholar
  25. Jauhari PK et al (2008) Synthesis of some novel 2-substituted benzoxazoles as anticancer, antifungal, and antimicrobial agents. Med Chem Res 17:412–424CrossRefGoogle Scholar
  26. Kumar O (2012) Design, synthesis, and anticonvulsant evaluation of some novel 1,3 benzothiazol-2-yl hydrazones/acetohydrazones. Med Chem Res 21:2428–2442CrossRefGoogle Scholar
  27. Morris GM et al (1998) Automated docking using a Lamarckian genetic algorithm and and empirical binding free energy function. J Comput Chem 19:1639–1662CrossRefGoogle Scholar
  28. Narasimhan B et al (2012) Benzimidazole: a medicinally important heterocyclic moiety. Med Chem Res 21:269–283CrossRefGoogle Scholar
  29. Petersson GA et al (1988) A complete basis set model chemistry. I. The total energies of closed-shell atoms and hydrides of the first-row elements. J Chem Phys 89:2193–2218CrossRefGoogle Scholar
  30. Reed AE, Weinhold F (1983) Natural bond orbital analysis of near-hartree-fock water dimer. J Chem Phys 78:4066–4073CrossRefGoogle Scholar
  31. Reed AE et al (1985) Natural population analysis. J Chem Phys 83:735–747CrossRefGoogle Scholar
  32. Reed AE et al (1988) Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint. Chem Rev 88:899–926CrossRefGoogle Scholar
  33. Satyendra R et al (2012) In vitro antimicrobial and molecular docking of dichloro substituted benzoxazole derivatives. Med Chem Res. doi: 10.1007/s00044-011-9963-z Google Scholar
  34. Silva SS et al (2012) Molecular dynamics simulations of peptide inhibitors complexed with Trypanosoma cruzi Trypanothione reductase. Chem BiolDrug Des. doi: 10.1111/j.1747-0285.2012.01429.x
  35. Stephens PJ, Devlin FJ, Chabalowski CF, Frisch MJ (1994) Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields. J Phys Chem 98:11623–11627CrossRefGoogle Scholar
  36. Taki M et al (2004) Emission ratiometric imaging of intracellular zinc: design of a benzoxazole fluorescent sensor and its application in two-photon microscopy. J Am Chem Soc 126:712–713PubMedCrossRefGoogle Scholar
  37. Tauer E, Grellmann KH (1990) Photochemical dehydrogenation, ring contraction, and ring expansion of hydrogenated derivatives of benzoxazino-benzoxazine, quinoxalino-quinoxaline, and bibenzothiazole. Chem Ber 123:1149–1154CrossRefGoogle Scholar
  38. Taylor EC et al (1986) Thallium in organic synthesis. 65. A novel synthesis of benzoxazoles from anilides. J Org Chem 51:1607–1609CrossRefGoogle Scholar
  39. Trujillo JG et al (2004) (2004) The E and Z isomers of 3-(benzoxazol-2-yl)prop-2-enoic acid. Acta Crystallogr C 60(Pt 10):o723–o726CrossRefGoogle Scholar
  40. Wolfe JF, Aronold FE (1981) Rigid-rod polymers. 1. Synthesis and thermal properties of para-aromatic polymers with 2,6-benzobisoxazole units in the main chain. Macromolecules 14:909–915CrossRefGoogle Scholar
  41. World Health Organization (WHO) (2012) Chagas disease (American trypanosomiasis). http://www.who.int/mediacentre/factsheets/fs340/en/index.html. Accessed 09 Sep 2012
  42. Yang G et al (2001) A new synthetic route to benzoxazole polymer via tandem Claisen rearrangement. Macromolecules 34:6545–6547CrossRefGoogle Scholar
  43. Yoshifuji M et al (1978) Preparation of benzoxazoles from n-alkylidene-2-hydroxyanilines and silver-oxide. Heterocycles 10:57–60CrossRefGoogle Scholar

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

Personalised recommendations