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
| Autor: | Jose L. Medina-Franco, Paolo Paoli, Carlos Nava-Zuazo, Samuel Estrada-Soto, Giovanni Camici, Gabriel Navarrete-Vazquez, Rolffy Rubén Ortiz Andrade, Marleth Ramírez Martínez, Jaime Escalante, Fabian Lopez-Vallejo |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Models Molecular Protein Conformation Stereochemistry In silico Drug Evaluation Preclinical Chemistry Techniques Synthetic Catalysis Glibenclamide chemistry.chemical_compound Drug Discovery medicine Animals Humans Hypoglycemic Agents Benzothiazoles Enzyme Inhibitors Rats Wistar Protein Tyrosine Phosphatase Non-Receptor Type 1 Pharmacology Hydrogen bond Organic Chemistry Computational Biology General Medicine Glucose Tolerance Test Protein Tyrosine Phosphatase 1B In vitro Rats Diabetes Protein tyrosine phosphatase PTP-1B Benzothiazole chemistry Biochemistry Docking (molecular) medicine.drug |
| Zdroj: | European Journal of Medicinal Chemistry. 53:346-355 |
| ISSN: | 0223-5234 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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