PTP1B inhibitory effects of tridepside and related metabolites isolated from the Antarctic lichen Umbilicaria antarctica.
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.
Seo
Changon
C
College of Medical and Life Sciences, Silla University, Sasang-gu, Busan 617-736, Republic of Korea.
Choi
Yun-Hyeok
YH
Ahn
Jong Seog
JS
Yim
Joung Han
JH
Lee
Hong Kum
HK
Oh
Hyuncheol
H
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
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