Novel Imbricatolic acid derivatives as protein tyrosine phosphatase-1B inhibitors: Design, synthesis, biological evaluation and molecular docking

Bioorganic & Medicinal Chemistry Letters
2016.0

Abstract

Protein tyrosine phosphatase (PTP-1B) antagonizes insulin signaling and is a potential therapeutic target for insulin resistance associated with obesity and type 2 diabetes. To find potential PTP-1B inhibitors, derivatives of Imbricatolic acid (1) have been synthesized by introducing various nitrogenous functionalities at C-15 and C-19 positions. They were evaluated for PTP-1B enzyme inhibition activity. Compounds 3, 6, 14, and 15 exhibited promising PTP-1B inhibitory activity at 10 μM concentrations with IC50 6.3, 6.8, 7.0 and 7.8 values, respectively. Structure activity relationship and molecular docking studies of these derivatives demonstrated that the integrity of the polar substituents were important for significant PTP-1B inhibitory activity. The Imbricatolic acid and active derivatives in this study might represent a starting point for development of new potential PTP-1B inhibitors.

DOI： 10.1016/j.bmcl.2016.03.003

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