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

European Journal of Medicinal Chemistry
Gabriel Navarrete-VázquezRolffy Ortiz-Andrade

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.

References

Mar 4, 2000·The Journal of Biological Chemistry·H S AndersenN P Møller
Apr 8, 2003·Current Topics in Medicinal Chemistry·Chidambaram Ramachandran, Brian P Kennedy
Jul 23, 2003·Current Medicinal Chemistry·Gang Liu
Feb 3, 2007·Journal of Computational Chemistry·Ruth HueyDavid S Goodsell
May 1, 2007·Drug Discovery Today·Sheng Zhang, Zhong-Yin Zhang

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Citations

Mar 19, 2013·Future Medicinal Chemistry·Ahmed Mehanna
Dec 3, 2014·European Journal of Medicinal Chemistry·Rangappa S KeriSrinivasa Budagumpi
Jan 4, 2017·Bioorganic Chemistry·Mansi VermaVipin K Garg
Dec 21, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marie Jazmín Sarabia-SánchezAlfredo Téllez-Valencia
Sep 28, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Sergio Hidalgo-FigueroaGabriel Navarrete-Vázquez

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