New prenylated isoflavonoids as protein tyrosine phosphatase 1B (PTP1B) inhibitors from Erythrina addisoniae

Phi Hung Nguyen; Govinda Sharma; Trong Tuan Dao; Mohammad Nasir Uddin; Keon Wook Kang; Derek Tantoh Ndinteh; Joseph Tanyi Mbafor; Won Keun Oh

doi:10.1016/j.bmc.2012.08.024

New prenylated isoflavonoids as protein tyrosine phosphatase 1B (PTP1B) inhibitors from Erythrina addisoniae

Bioorg Med Chem. 2012 Nov 1;20(21):6459-64. doi: 10.1016/j.bmc.2012.08.024. Epub 2012 Sep 7.

Authors

Phi Hung Nguyen¹, Govinda Sharma, Trong Tuan Dao, Mohammad Nasir Uddin, Keon Wook Kang, Derek Tantoh Ndinteh, Joseph Tanyi Mbafor, Won Keun Oh

Affiliation

¹ Korea Bioactive Natural Material Bank, College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759, Republic of Korea.

PMID: 23022281
DOI: 10.1016/j.bmc.2012.08.024

Abstract

Bioassay-guided fractionation of the EtOAc extract of the root of Erythrina addisoniae (Leguminosae) resulted in the isolation of four new (1-4), along with 2 known prenylated isoflavonoids (5-6). The structures of the isolates were assigned on the basis of spectroscopic data analysis, focusing on interpretation of 1D and 2D NMR, and MS data. All the isolates were evaluated for their inhibitory effects on protein tyrosine phosphatase 1B (PTP1B), as well as their growth inhibition on MCF7, adriamycin-resistant MCF7 (MCF7/ADR), and MDA-MB-231 breast cancer cell lines. Compounds which exhibited PTP1B inhibitory activity (IC(50) values ranging from 4.6 ± 0.3 to 24.2 ± 2.1 μM) showed potential cytotoxic activity (IC(50) values ranging from 3.97 ± 0.17 to 11.4 ± 1.9 μM). Taken together, our data suggest that prenylated isoflavonoids, especially the isoflavone-type skeleton could be considered as new lead compounds against breast cancer via PTP1B inhibition.

Publication types

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

MeSH terms

Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / isolation & purification
Antineoplastic Agents, Phytogenic / pharmacology*
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / isolation & purification
Enzyme Inhibitors / pharmacology*
Erythrina / chemistry*
Humans
Isoflavones / chemistry
Isoflavones / isolation & purification
Isoflavones / pharmacology*
MCF-7 Cells
Molecular Structure
Plant Extracts / chemistry
Plant Roots / chemistry
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Recombinant Proteins / antagonists & inhibitors
Recombinant Proteins / metabolism
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Isoflavones
Plant Extracts
Recombinant Proteins
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1