Synthesis and biological activity of fibrate-based acyl- and alkyl-phenoxyacetic methyl esters and 1,2-dihydroquinolines
Por:
Pucheta A., Mendieta A., Madrigal D.A., Hernández-Benitez R.I., Romero L., Garduño-Siciliano L., Rugerio-Escalona C., Cruz-López M.C., Jiménez F., Ramírez-Villalva A., Fuentes-Benites A., González-Romero C., Gómez-García O., López J., Vázquez M.A., Rosales-Acosta B., Villa-Tanaca L., Sequeda-Juárez A., Ramón-Gallegos E., Chamorro-Cevallos G., Delgado F., Tamariz J.
Publicada:
1 ene 2020
Resumen:
A series of highly potent antihyperlipidemic agents constituted by a fibrate-based structure was recently reported by our group, whose synthesis started from isovanillin derivatives. In the interest of evaluating the bioisosteric effect of the vanillin-based isomers on their antihyperlipidemic activity, the present study focuses on the synthesis of 5-acyl-1-phenoxyacetic methyl esters 5a–c and their saturated side-chain 5-alkyl-1-phenoxyacetates 6a–c. Their strong in vivo effect was associated with the inhibition of HMG-CoA reductase. Since 1,2-dihydroquinolines inhibit this enzyme, a series of such heterocycles (9a–d) was prepared by our efficient regioselective, one-step, solvent-free method. Apart from showing hypolipidemic activity in vivo, some of the compounds displayed antifungal, antioxidant and cytotoxic activity in vitro. The binding mode of four compounds at the active site of HMGRh was examined with docking simulations, observing an interaction with most of the amino acids targeted by simvastatin. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Filiaciones:
Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional (IPN). Prol. Carpio y Plan de Ayala S/N, Mexico City, 11340, Mexico
Departamento de Farmacia, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Av. Wilfrido Massieu S/N, Unidad Adolfo López Mateos, Mexico City, 07738, Mexico
Centro de Investigación en Biotecnología Aplicada, IPN. Carretera Estatal Santa Inés Tecuexcomac-Tepetitla, Km 1.5, Tepetitla de Lardizábal, Tlaxcala, 90700, Mexico
Departamento de Química Orgánica, Facultad de Química, Universidad Autónoma del Estado de México (UAEM), Paseo Tollocan y Colón S/N, Toluca, 50000, Mexico
Departamento de Química, Universidad de Guanajuato, Noria Alta S/N, Guanajuato, Gto 36050, Mexico
Laboratorio de Genética Microbiana, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. Carpio y Plan de Ayala S/N, Mexico City, 11340, Mexico
Departamento de Morfología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Av. Wilfrido Massieu S/N, Unidad Adolfo López Mateos, Mexico City, 07738, Mexico
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