Protein Tyrosine Phosphatase-1B Inhibitory Activity of Isoprenylated Flavonoids Isolated from Erythrina mildbraedii

摘要

Inhibition of protein tyrosine phosphatase-1B(PTP1B)has been proposed as a therapy for treatment of type-2 diabetes and obesity.Bioassay-guided fractionation of an EtOAc-soluble extract of the root bark of Erythrina mildbraedii,using an in vitro PTP1B inhibitory assay,resulted in the isolation of three new isoprenylated flavonoids,abyssinone-IV-4'-O-methyl ether(2),7-hydroxy-4'-methoxy-3'-(3-hydroxy-3-methyl-trans-but-1-enyl)-5'-(3-methylbut-2-enyl)flavanone(3),and abyssinone-VI-4-O-methyl ether(6),along,with six known flavonoids,abyssinone-V-4'-O-methyl ether(1),abyssinone-V(4),abyssinone-IV(5),sigmoidin E(7),4'-hydroxy-5,7-dimethoxyisoflavone(8),and alpinumisoflavone(9).Compounds 1 and 2,4-7,and 9 inhibited PTP1B activity,with IC_(50)values ranging from 14.8 +-1.1 to 39.7 +-2.5 mu M.On the basis of the data obtained,flavanones and chalcones with isoprenyl groups may be considered as a new class of PTP1B inhibitors.