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 IB (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-(γ, γ-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 IC50 values ranging from 2.6 ± 0.5 to 10.1 ± 0.3 μM. 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. © Georg Thieme Verlag KG Stuttgart.