PTP1B inhibitors from the seeds of Iris sanguinea and their insulin mimetic activities via AMPK and ACC phosphorylation

• Published in: Bioorganic & medicinal chemistry letters 2017-11, Vol.27 (22), p.5076-5081
• Main Authors: Yang, Jun Li, Ha, Thi Kim Quy, Lee, Ba Wool, Kim, Jinwoong, Oh, Won Keun
• Format: Article
• Language: English
• Subjects: Acetyl-CoA Carboxylase - metabolism; AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Binding Sites; Biological Products - chemistry; Biological Products - isolation & purification; Biological Products - pharmacology; Cell Line; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Glucose - metabolism; Glucose uptake; Insulins - chemistry; Iris - chemistry; Iris - metabolism; Iris sanguinea; Magnetic Resonance Spectroscopy; Mice; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Molecular Conformation; Molecular Docking Simulation; Phosphorylation - drug effects; Plant Extracts - chemistry; Protein Structure, Tertiary; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism; PTP1B; Seeds - chemistry; Seeds - metabolism; Signal Transduction - drug effects; Triterpene
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.09.031

[Display omitted] To find PTP1B inhibitors from natural products, two new compounds (1 and 2), along with nine known compounds (3–11), were isolated from a methanol-soluble extract of Iris sanguinea seeds. The structures of compounds 1 and 2 were determined based on extensive spectroscopic data analysis including UV, IR, NMR, and MS. The IC50 value of compound 5 on protein tyrosine phosphatase 1B (PTP1B) inhibitory activity is 7.30±0.88µM with a little activity compared to the IC50 values of the tested positive compound. Compound 5 significantly enhanced glucose uptake and activation of pACC, pAMPK and partially Erk1/2 signaling. These results suggest that compound 5 from Iris sanguinea seeds are utilized as both PTP1B inhibitors and regulators of glucose uptake. These beneficial effects could be applied to treat metabolic diseases such as diabetes and obesity.