Protein tyrosine phosphatase 1B inhibitors isolated from Morus bombycis

• Published in: Bioorganic & medicinal chemistry letters 2009-12, Vol.19 (23), p.6759-6761
• Main Authors: Hoang, Duc Manh, Ngoc, Tran Minh, Dat, Nguyen Tien, Ha, Do Thi, Kim, Young Ho, Luong, Hoang Van, Ahn, Jong Seog, Bae, KiHwan
• Format: Article
• Language: English
• Subjects: 2-Arylbenzofuran derivatives; Benzofurans - chemistry; Benzofurans - isolation & purification; Benzofurans - pharmacology; Biological and medical sciences; Chalcone-derived Diels–Alder types; Drug Design; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; General pharmacology; Medical sciences; Molecular Structure; Morus - chemistry; Morus bombycis; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Protein tyrosine phosphatase 1B (PTP1B); Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors; Stereoisomerism; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.09.102

Inhibitory constituents against protein tyrosine phosphatase 1B from Morus bombycis. Bioassay-guided fractionation of the chloroform-soluble fraction of Morus bombycis, using an in vitro PTP1B inhibitory assay led to the identification of three 2-arylbenzofurans, albafuran A ( 1), mulberrofuran W ( 2) and mulberrofuran D ( 6), along with three chalcone-derived Diels–Alder products, kuwanon J ( 3), kuwanon R ( 4), and kuwanon V ( 5). Compounds 1– 6 showed remarkable inhibitory activity against PTP1B with IC 50 values ranging from 2.7 to 13.8 μM. Inhibition kinetics were analyzed by Lineweaver–Burk plots, which suggested that compounds 1– 6 inhibited PTP1B in a mixed-type manner. The present results indicate that the respective lipophilic and hydroxyl groups of 2-arylbenzofurans and chalcone-derived Diels–Alder products play an important role in inhibition of PTP1B.