TY - JOUR
T1 - Synthesis and theoretic calculations of benzoxazoles and docking studies of their interactions with triosephosphate isomerase
AU - Flores Sandoval, César A.
AU - Cuevas Hernández, Roberto I.
AU - Correa Basurto, José
AU - Beltrán Conde, Hiram I.
AU - Padilla Martínez, Itzia I.
AU - Farfán García, José N.
AU - Nogueda Torres, Benjamín
AU - Trujillo Ferrara, José G.
N1 - Funding Information:
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.
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
KW - Molecular docking
KW - Molecular modeling
KW - Stereoisomers
KW - Triosephophate isomerase
UR - http://www.scopus.com/inward/record.url?scp=84879694525&partnerID=8YFLogxK
U2 - 10.1007/s00044-012-0264-y
DO - 10.1007/s00044-012-0264-y
M3 - Artículo
SN - 1054-2523
VL - 22
SP - 2768
EP - 2777
JO - Medicinal Chemistry Research
JF - Medicinal Chemistry Research
IS - 6
ER -