Inhibition of protein tyrosine phosphatase 1B by prenylated isoflavonoids isolated from the stem bark of Erythrina addisoniae

• Published in: Planta medica Vol. 72; no. 10; pp. 945 - 948
• Main Authors: Bae, E.Y, Na, M, Njamen, D, Mbafor, J.T, Formum, Z.T, Cui, L, Choung, D.H, Kim, B.Y, Oh, W.K, Ahn, J.S
• Format: Journal Article
• Language: English
• Published: Germany 01.08.2006
• Subjects: chemical structure; enzyme inhibition; enzyme inhibitors; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Erythrina; Erythrina - chemistry; Erythrina addisoniae; Fabaceae; human health; Humans; Isoflavones - chemistry; Isoflavones - isolation & purification; Isoflavones - pharmacology; isoflavonoids; noninsulin-dependent diabetes mellitus; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Stems - chemistry; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases - antagonists & inhibitors; protein-tyrosine-phosphatase; spectral analysis; structure-activity relationships; Cameroon
• ISSN: 0032-0943; 1439-0221
• DOI: 10.1055/s-2006-946674

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.