New 5-deoxyflavonoids and their inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) activity

TY - JOUR

T1 - New 5-deoxyflavonoids and their inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) activity

AU - Nguyen, Phi Hung

AU - Dao, Trong Tuan

AU - Kim, Jayeon

AU - Phong, Do Tuan

AU - Ndinteh, Derek Tantoh

AU - Mbafor, Joseph Tanyi

AU - Oh, Won Keun

N1 - Copyright © 2011 Elsevier Ltd. All rights reserved.

PY - 2011/6/1

Y1 - 2011/6/1

N2 - In the course of our program to search for protein tyrosine phosphatase 1B (PTPB) inhibitors, five new 5-deoxyflavonoids along with eight known derivatives were isolated from EtOAc layer of the root bark of Erythrina abyssinica. Their structures were elucidated on the basis of spectroscopic (IR, UV, MS, CD, 1D- and 2D-NMR) and physicochemical analyses. All isolates exhibited moderate inhibitory effects on the enzyme assay with IC50 values ranging from 14.9 ± 1.6 to 98.1 ± 11.3 μM. Compounds with prenyl and methoxy groups in the B ring (1, 2, 4, 8, and 13) possessed strong activity (IC 50 14.9 ± 1.6 to 19.2 ± 1.1 μM), while compounds (3, 5, and 9) with 2,2-dimethylpyrano ring showed less inhibitory effect (IC 50 22.6 ± 2.3 to 72.9 ± 9.7 μM). These results suggest that prenyl and methoxy groups may be responsible for the increase on the activity of 5-deoxyflavonoids against PTP1B, but the presence of 2,2-dimethylpyrano ring on the B ring may be induced the decrease of PTP1B inhibitory activity.

AB - In the course of our program to search for protein tyrosine phosphatase 1B (PTPB) inhibitors, five new 5-deoxyflavonoids along with eight known derivatives were isolated from EtOAc layer of the root bark of Erythrina abyssinica. Their structures were elucidated on the basis of spectroscopic (IR, UV, MS, CD, 1D- and 2D-NMR) and physicochemical analyses. All isolates exhibited moderate inhibitory effects on the enzyme assay with IC50 values ranging from 14.9 ± 1.6 to 98.1 ± 11.3 μM. Compounds with prenyl and methoxy groups in the B ring (1, 2, 4, 8, and 13) possessed strong activity (IC 50 14.9 ± 1.6 to 19.2 ± 1.1 μM), while compounds (3, 5, and 9) with 2,2-dimethylpyrano ring showed less inhibitory effect (IC 50 22.6 ± 2.3 to 72.9 ± 9.7 μM). These results suggest that prenyl and methoxy groups may be responsible for the increase on the activity of 5-deoxyflavonoids against PTP1B, but the presence of 2,2-dimethylpyrano ring on the B ring may be induced the decrease of PTP1B inhibitory activity.

KW - Circular Dichroism

KW - Enzyme Inhibitors

KW - Erythrina

KW - Flavonoids

KW - Humans

KW - Magnetic Resonance Spectroscopy

KW - Molecular Conformation

KW - Plant Bark

KW - Plant Roots

KW - Protein Tyrosine Phosphatase, Non-Receptor Type 1

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.bmc.2011.04.037

DO - 10.1016/j.bmc.2011.04.037

M3 - Journal article

C2 - 21571537

SN - 0968-0896

VL - 19

SP - 3378

EP - 3383

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 11

ER -