A para-amino substituent on the D-ring of green tea polyphenol epigallocatechin-3-gallate as a novel proteasome inhibitor and cancer cell apoptosis inducer

Kumi Osanai; Kristin R Landis-Piwowar; Q Ping Dou; Tak Hang Chan

doi:10.1016/j.bmc.2007.05.041

A para-amino substituent on the D-ring of green tea polyphenol epigallocatechin-3-gallate as a novel proteasome inhibitor and cancer cell apoptosis inducer

Bioorg Med Chem. 2007 Aug 1;15(15):5076-82. doi: 10.1016/j.bmc.2007.05.041. Epub 2007 May 18.

Authors

Kumi Osanai¹, Kristin R Landis-Piwowar, Q Ping Dou, Tak Hang Chan

Affiliation

¹ Department of Applied Biology and Chemical Technology and the Open Laboratory of Chirotechnology, Institute of Molecular Technology for Drug Discovery and Synthesis, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, SAR, China.

Abstract

Analogs of (-)-EGCG containing a para-amino group on the D-ring in place of the hydroxyl groups have been synthesized and their proteasome inhibitory activities were studied. We found that, the O-acetylated (-)-EGCG analogs possessing a p-NH(2) or p-NHBoc (Boc; tert-butoxycarbonyl) D-ring (5 and 7) act as novel tumor cellular proteasome inhibitors and apoptosis inducers with potency similar to natural (-)-EGCG and similar to (-)-EGCG peracetate. These data suggest that the acetylated amino-GTP analogs have the potential to be developed into novel anticancer agents.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects
B-Lymphocytes / drug effects
Caspase 3 / metabolism
Catechin / analogs & derivatives*
Catechin / chemistry
Catechin / pharmacology
Cell Line, Tumor
Humans
Leukemia / drug therapy
Molecular Structure
Proteasome Endopeptidase Complex / metabolism
Structure-Activity Relationship
Tea / chemistry*

Substances

Tea
Catechin
epigallocatechin gallate
Caspase 3
Proteasome Endopeptidase Complex

Abstract

Publication types

MeSH terms

Substances

Grants and funding