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

Abstract

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.