Inhibition of protein tyrosine phosphatase 1B by prenylated isoflavonoids isolated from the stem bark of Erythrina addisoniae.
It has been suggested that protein tyrosine phosphatase 1B (PTP1B) inhibitors might be a therapeutic target for the treatment of type 2 diabetes and obesity. A bioassay-guided phytochemical study of the EtOAc extract of the stem bark of Erythrina addisoniae (Leguminosae) resulted in the identification of a new PTP1B inhibitory compound, 5,2',4'-trihydroxy-6-(gamma,gamma-dimethylallyl)-2''',2'''-dimethyldihydropyrano[5''',6''']isoflavanone ( 6), along with five known prenylated isoflavonoids, orientanol E ( 1), senegalensin ( 2), warangalone ( 3), warangalone 4'-methyl ether ( 4) and 2,3-dihydroauriculatin ( 5). Compounds 1, 5 and 6 inhibited PTP1B with IC (50) values ranging from 2.6 +/- 0.5 to 10.1 +/- 0.3 microM. Our results indicate that hydroxylation at both 2'- and 4'-positions in the B-ring and cyclization between a hydroxy group at C-7 and one of the prenyl groups at C-6 or C-8 in the A-ring may be important for activity. Thus, compounds 5 and 6 could be a new class of natural PTP1B inhibitors.
Bae
Eun Young
EY
Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Korea.
Na
Minkyun
M
Njamen
Dieudonné
D
Mbafor
Joseph Tanyi
JT
Fomum
Zacharias Tanee
ZT
Cui
Long
L
Choung
Dong Ho
DH
Kim
Bo Yeon
BY
Oh
Won Keun
WK
Ahn
Jong Seog
JS
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004895:Erythrina / Q000737:chemistry*; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018547:Plant Stems / Q000737:chemistry; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D007529:Isoflavones; D010936:Plant Extracts; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases