Protein tyrosine phosphatase 1B inhibitory activity of triterpenes isolated from Astilbe koreana.
Bioassay-guided fractionation of a MeOH extract of the rhizomes of Astilbe koreana (Saxifragaceae), using an in vitro protein tyrosine phosphatase 1B (PTP1B) inhibitory assay, resulted in the isolation of a new triterpene, 3alpha,24-dihydroxyolean-12-en-27-oic acid (4), along with four triterpenes, 3-oxoolean-12-en-27-oic acid (1), 3beta-hydroxyolean-12-en-27-oic acid (beta-peltoboykinolic acid; 2), 3beta-hydroxyurs-12-en-27-oic acid (3), and 3beta,6beta-dihydroxyolean-12-en-27-oic acid (astilbic acid; 5). Compounds 1-5 inhibited PTP1B with IC50 values of 6.8+/-0.5, 5.2+/-0.5, 4.9+/-0.4, 11.7+/-0.9, and 12.8+/-1.1 microM, respectively. Our results indicate that 3-hydroxyl group and a carboxyl group in this type of triterpenes may be required for the activity, while addition of one more hydroxyl group at C-6 or C-24 may be responsible for a loss of activity. Thus, compounds 2 and 3 which possess only one hydroxyl group at C-3 and a carboxyl group at C-27 could be potential PTP1B inhibitors.
Na
MinKyun
M
Korea Research Institute of Bioscience and Biotechnology, 52 Eoun-dong, Yuseong-gu, Daejeon 305-333, Republic of Korea.
Cui
Long
L
Min
Byung Sun
BS
Bae
KiHwan
K
Yoo
Jae Kuk
JK
Kim
Bo Yeon
BY
Oh
Won Keun
WK
Ahn
Jong Seog
JS
D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D031995:Saxifragaceae / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014315:Triterpenes; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases