title: PTP1B inhibitory effects of tridepside and related metabolites isolated from the Antarctic lichen Umbilicaria antarctica.
abstract: The selective inhibition of PTP1B has been widely recognized as a potential drug target for the treatment of type 2 diabetes and obesity. In the course of screening for PTP1B inhibitory natural products, the MeOH extract of the dried sample of the Antarctic lichen Umbilicaria antarctica was found to exhibit significant inhibitory effect, and the bioassay-guided fractionation and purification afforded three related lichen metabolites 1-3. Compounds 1-3 were identified as gyrophoric acid (1), lecanoric acid (2), and methyl orsellinate (3) mainly by analysis of NMR and MS data. These compounds inhibited PTP1B activity with 50% inhibitory concentration values of 3.6 +/- 0.04 microM, 31 +/- 2.7 microM, and 277 +/- 8.6 microM, respectively. Furthermore, the kinetic analysis of PTP1B inhibition by compound 1 suggested that the compound inhibited PTP1B activity in a non-competitive manner.
authors.affiliation: College of Medical and Life Sciences, Silla University, Sasang-gu, Busan 617-736, Republic of Korea.
authors.forename: Changon
authors.initials: C
authors.lastname: Seo
authors.forename: Yun-Hyeok
authors.initials: YH
authors.lastname: Choi
authors.forename: Jong Seog
authors.initials: JS
authors.lastname: Ahn
authors.forename: Joung Han
authors.initials: JH
authors.lastname: Yim
authors.forename: Hong Kum
authors.initials: HK
authors.lastname: Lee
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
mesh_terms: D000864:Antarctic Regions; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D008011:Lichens / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D012118:Resorcinols / Q000737:chemistry / Q000494:pharmacology; D012459:Salicylates / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001565:Benzoates; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D012118:Resorcinols; D012459:Salicylates; C472106:methyl orsellinate; C008263:lecanoric acid; C120727:gyrophoric acid; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1