title: Novel chromenedione derivatives displaying inhibition of protein tyrosine phosphatase 1B (PTP1B) from Flemingia philippinensis.
abstract: 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.
authors.affiliation: College of Food and Biological Engineering, Qiqihar University, Qiqihar 161006, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Applied Life Science (BK21 Plus), IALS, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Heung Joo
authors.initials: HJ
authors.lastname: Yuk
authors.affiliation: Division of Applied Life Science (BK21 Plus), IALS, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Jeong Yoon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Division of Applied Life Science (BK21 Plus), IALS, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Dae Wook
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Division of Applied Life Science (BK21 Plus), IALS, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Yeong Hun
authors.initials: YH
authors.lastname: Song
authors.affiliation: Division of Applied Life Science (BK21 Plus), IALS, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Xue Fei
authors.initials: XF
authors.lastname: Tan
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, United States.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Curtis-Long
authors.affiliation: Division of Applied Life Science (BK21 Plus), IALS, Gyeongsang National University, Jinju 660-701, Republic of Korea. Electronic address: khpark@gnu.ac.kr.
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Park
mesh_terms: D007887:Fabaceae / Q000737:chemistry*; D047309:Flavones / Q000737:chemistry* / Q000302:isolation & purification; D045782:Hemiterpenes / Q000737:chemistry* / Q000302:isolation & purification; D007700:Kinetics; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D047309:Flavones; D045782:Hemiterpenes; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Chromenedione derivatives; Flemingia philippinensis; Philippin A, B, C; Protein tyrosine phosphatase 1B (PTP1B)