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

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.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Benzothiazole provoked PTP-1B inhibition in the low micro-molar range. ► Docking analysis with PTP-1B suggested the potential binding of compounds into the catalytic site. ► Compounds induced in vivo hypoglycemic effects.