title: PTP1B inhibitory activity of kaurane diterpenes isolated from Siegesbeckia glabrescens.
abstract: Protein tyrosine phosphatase 1B (PTP1B) is considered as a therapeutic target for the treatment of diabetes and obesity. In our preliminary screening study, a MeOH extract of the aerial part of Siegesbeckia glabrescens was found to inhibit PTP1B activity at 30 microg/mL. Bioassay-guided fractionation led to the isolation of two active diterpenes, ent-16betaH, 17-isobutyryloxy-kauran-19-oic acid (1) and ent-16betaH, 17-acetoxy-18-isobutyryloxy-kauran-19-oic acid (2), along with ent- 16betaH, 17-hydroxykauran-19-oic acid (3). Compounds 1 and 2 inhibited the PTP1B activity with IC50 values of 8.7 +/- 0.9 and 30.6 +/- 2.1 microM, respectively. Kinetic studies suggest that both 1 and 2 are non-competitive inhibitors of PTP1B. However, compound 3 substituted with a hydroxyl group at C-17 in kaurane-type showed no inhibitory effects towards PTP1B.
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, 52 Eoun-dong, Yuseong-gu, Daejeon 305-333 Korea, South Korea.
authors.forename: Sohee
authors.initials: S
authors.lastname: Kim
authors.forename: Minkyun
authors.initials: M
authors.lastname: Na
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
authors.forename: Junpil
authors.initials: J
authors.lastname: Jang
authors.forename: Cheon Bae
authors.initials: CB
authors.lastname: Sohn
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Won Keun
authors.initials: WK
authors.lastname: Oh
authors.forename: Jong Seog
authors.initials: JS
authors.lastname: Ahn
mesh_terms: D019659:Asteraceae / Q000378:metabolism*; D045786:Diterpenes, Kaurane / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D010936:Plant Extracts / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D045786:Diterpenes, Kaurane; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011994:Recombinant Proteins; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases