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: Sohee Kim, Minkyun Na, Hyuncheol Oh, Junpil Jang, Cheon Bae Sohn, Bo Yeon Kim, Won Keun Oh, Jong Seog Ahn
• Journal: Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem) Vol. 21 Issue 4 Pg. 379-83 (Aug 2006) ISSN: 1475-6366 [Print] England
• PMID: 17059169 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diterpenes, Kaurane
• Enzyme Inhibitors
• Plant Extracts
• Recombinant Proteins
• PTPN1 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 1
• Protein Tyrosine Phosphatases

Topics

• Asteraceae (metabolism)
• Diterpenes, Kaurane (chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• Enzyme Inhibitors (pharmacology)
• Humans
• Inhibitory Concentration 50
• Kinetics
• Models, Chemical
• Plant Extracts (metabolism)
• Protein Tyrosine Phosphatase, Non-Receptor Type 1
• Protein Tyrosine Phosphatases (antagonists & inhibitors, chemistry)
• Recombinant Proteins (chemistry)