Novel chromenedione derivatives displaying inhibition of protein tyrosine phosphatase 1B (PTP1B) from Flemingia philippinensis

• Published in: Bioorganic & medicinal chemistry letters 2016-01, Vol.26 (2), p.318-321
• Main Authors: Wang, Yan, Yuk, Heung Joo, Kim, Jeong Yoon, Kim, Dae Wook, Song, Yeong Hun, Tan, Xue Fei, Curtis-Long, Marcus J., Park, Ki Hun
• Format: Article
• Language: English
• Subjects: Chromenedione derivatives; Fabaceae - chemistry; Flavones - chemistry; Flavones - isolation & purification; Flemingia philippinensis; Hemiterpenes - chemistry; Hemiterpenes - isolation & purification; Kinetics; Philippin A, B, C; Protein tyrosine phosphatase 1B (PTP1B); Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - chemistry
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.12.021

[Display omitted] Protein tyrosine phosphatase 1B (PTP1B) is an important target to treat obesity and diabetes due to its key roles in insulin and leptin signaling. The MeOH extracts of the root bark of Flemingia philippinensis yielded eight inhibitory molecules (1–8) capable of targeting PTP1B. Three of them were identified to be novel compounds, philippin A (1), philippin B (2), and philippin C (3) which have a rare 3-phenylpropanoyl chromenedione skeleton. The other compounds (4–8) were known prenylated isoflavones. All compounds (1–8) inhibited PTP1B in a dose dependent manner with IC50s ranging between 2.4 and 29.4μM. The most potent compound emerged to be prenylated isoflavone 5 (IC50=2.4μM). In kinetic studies, chromenedione derivatives (1–3) emerged to be reversible, competitive inhibitors, whereas prenylated isoflavones (5–8) were noncompetitive inhibitors.