Aglaiabbrevins A–D, New Prenylated Bibenzyls from the Leaves of Aglaia abbreviata with Potent PTP1B Inhibitory Activity

摘要

Four new prenylated bibenzyls, named aglaiabbrevins A–D ( 2 , 4 – 6 ), were isolated from the leaves of Aglaia abbreviata , along with two known related analogues, 3,5-dihydroxy-2-[3,7-dimethyl-2( E ),6-octadienyl]bibenzyl ( 7 ) and 3,5-dihydroxy-2-(3-methyl-2-butenyl)bibenzyl ( 8 ). The structures of the new compounds were elucidated on the basis of extensive spectroscopic experiments, mainly one and two dimensional (1D- and 2D)-NMR, and the absolute configuration of 5 was determined by the measurement of specific rotation. The isolated compounds were evaluated for their protein tyrosine phosphatase-1B (PTP1B) inhibitory activity. The results showed that compounds 5 – 7 exhibited more potent PTP1B inhibitory effects with IC₅₀ values of 2.58±0.52, 2.44±0.35, and 2.23±0.14?μM, respectively, than the positive control oleanolic acid (IC₅₀=2.74±0.20?μM). On the basis of the data obtained, these bibenzyls with the longer C-2 prenyl groups may be considered as potential lead compounds for the development of new anti-obesity and anti-diabetic agents. Also, the PTP1B inhibitory effects for prenylated bibenzyls are being reported for the first time.