Synthesis, in vitro and in silico screening of ethyl 2-(6-substituted benzo[d]thiazol-2-ylamino)-2-oxoacetates as protein-tyrosine phosphatase 1B inhibitors
Por:
Navarrete-Vazquez G., Ramírez-Martínez M., Estrada-Soto S., Nava-Zuazo C., Paoli P., Camici G., Escalante-García J., Medina-Franco J.L., López-Vallejo F., Ortiz-Andrade R.
Publicada:
1 jul 2012
Resumen:
The ethyl 2-(6-substituted benzo[d]thiazol-2-ylamino)-2-oxoacetate derivatives (OX 1-9) were prepared using a one-step reaction. The in vitro inhibitory activity of the compounds against protein tyrosine phosphatase 1B (PTP-1B) was evaluated. Compounds OX-(1, 6 and 7) were rapid reversible (mixed-type) inhibitors of PTP-1B with IC50 values in the low micro-molar range. The most active compounds OX-(1, 6 and 7) were docked into the crystal structure of PTP-1B. Docking results indicate potential hydrogen bond interactions between the oxamate group in all compounds and the catalytic amino acid residues Arg221 and Ser216. The compounds were evaluated for their in vivo hypoglycemic activity, showing significant lowering of plasma glucose concentration in acute normoglycemic model and oral glucose tolerance test similarly at the effect exerted for hypoglycemic drug glibenclamide. (C) 2012 Elsevier Masson SAS. All rights reserved.
Filiaciones:
Navarrete-Vazquez G.:
Facultad de Farmacia, Universidad Autónoma Del Estado de Morelos, Av Universidad 1001, Chamilpa, Cuernavaca 62209, Morelos, Mexico
Ramírez-Martínez M.:
Facultad de Farmacia, Universidad Autónoma Del Estado de Morelos, Av Universidad 1001, Chamilpa, Cuernavaca 62209, Morelos, Mexico
Estrada-Soto S.:
Facultad de Farmacia, Universidad Autónoma Del Estado de Morelos, Av Universidad 1001, Chamilpa, Cuernavaca 62209, Morelos, Mexico
Nava-Zuazo C.:
Facultad de Farmacia, Universidad Autónoma Del Estado de Morelos, Av Universidad 1001, Chamilpa, Cuernavaca 62209, Morelos, Mexico
Paoli P.:
Dipartimento di Scienze Biochimiche, Università Degli Studi di Firenze, Firenze 50134, Italy
Camici G.:
Dipartimento di Scienze Biochimiche, Università Degli Studi di Firenze, Firenze 50134, Italy
Escalante-García J.:
Centro de Investigaciones Químicas, Universidad Autónoma Del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico
Medina-Franco J.L.:
Torrey Pines Institute for Molecular Studies, Port St., Lucie, FL 34987, United States
López-Vallejo F.:
Torrey Pines Institute for Molecular Studies, Port St., Lucie, FL 34987, United States
Ortiz-Andrade R.:
Facultad de Química, Universidad Autónoma de Yucatán, Merida, Yucatán 97000, Mexico
All Open Access; Green
|