title: 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.
abstract: 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 IC(50) 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.
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av Universidad 1001, Chamilpa, Cuernavaca 62209, Morelos, Mexico. gabriel_navarrete@uaem.mx
authors.forename: Gabriel
authors.initials: G
authors.lastname: Navarrete-Vazquez
authors.forename: Marleth
authors.initials: M
authors.lastname: Ramírez-Martínez
authors.forename: Samuel
authors.initials: S
authors.lastname: Estrada-Soto
authors.forename: Carlos
authors.initials: C
authors.lastname: Nava-Zuazo
authors.forename: Paolo
authors.initials: P
authors.lastname: Paoli
authors.forename: Guido
authors.initials: G
authors.lastname: Camici
authors.forename: Jaime
authors.initials: J
authors.lastname: Escalante-García
authors.forename: José L
authors.initials: JL
authors.lastname: Medina-Franco
authors.forename: Fabian
authors.initials: F
authors.lastname: López-Vallejo
authors.forename: Rolffy
authors.initials: R
authors.lastname: Ortiz-Andrade
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D019295:Computational Biology; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008958:Models, Molecular; D011487:Protein Conformation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
chemical_list: D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C005465:benzothiazole