Synthesis and theoretic calculations of benzoxazoles and docking studies of their interactions with triosephosphate isom
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Med Chem Res (2013) 22:2768–2777 DOI 10.1007/s00044-012-0264-y
ORIGINAL RESEARCH
Synthesis and theoretic calculations of benzoxazoles and docking studies of their interactions with triosephosphate isomerase Ce´sar A. Flores Sandoval • Roberto I. Cuevas Herna´ndez • Jose´ Correa Basurto Hiram I. Beltra´n Conde • Itzia I. Padilla Martı´nez • Jose´ N. Farfa´n Garcı´a • Benjamı´n Nogueda Torres • Jose´ G. Trujillo Ferrara
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Received: 23 April 2012 / Accepted: 28 September 2012 / Published online: 20 October 2012 Ó Springer Science+Business Media New York 2012
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
Electronic supplementary material The online version of this article (doi:10.1007/s00044-012-0264-y) contains supplementary material, which is available to authorized users. C. A. Flores Sandoval Programa de ingenierı´a Molecular, Instituto Mexicano del Petro´leo, 07730 Mexico, DF, Mexico R. I. Cuevas Herna´ndez J. Correa Basurto J. G. Trujillo Ferrara (&) Laboratorio de Modelado Molecular y Bioinforma´tica, Departamento de Bioquı´mica, Escuela Superior de Medicina, Instituto Polite´cnico Nacional, 11340 Mexico, DF, Mexico e-mail: [email protected] H. I. Beltra´n Conde Departamento de Ciencias Naturales, UAM-Cuajimalpa, 11850 Mexico, DF, Mexico I. I. Padilla Martı´nez Unidad Profesional Interdisciplinaria de Biotecnologı´a, Instituto Polite´cnico Nacional, 07340 Mexico, DF, Mexico J. N. Farfa´n Garcı´a Departamento de Quı´mica, Facultad de Quı´mica, UNAM, Ciudad Universitaria, 04510 Mexico, DF, Mexico B. Nogueda Torres Departamento de Parasitologı´a, Escuela Nacional de Ciencias Biolo´gicas, Instituto Polite´cnico Nacional, 11340 Mexico, DF, Mexico
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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–HN 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 p–p 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
Introduction Benzoxazoles have been studied since 1959 for use in various scientific areas, including the synthesis of compounds em
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