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

被引：49

作者：

Osanai, Kumi

Landis-Piwowar, Kristin R.

Dou, Q. Ping

Chan, Tak Hang ^{[1
]}

机构：

[1] Hong Kong Polytech Univ, Inst Mol Technol Drug Discovery & Synthesis, Dept Appl Biol & Chem Technol, Hong Kong, Hong Kong, Peoples R China

[2] Hong Kong Polytech Univ, Inst Mol Technol Drug Discovery & Synthesis, Open Lab Chirotechnol, Hong Kong, Hong Kong, Peoples R China

[3] Wayne State Univ, Sch Med, Prevent Program, Barbana Ann Karmanos Canc Inst, Detroit, MI 48202 USA

[4] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48202 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2007年 / 15卷 / 15期

关键词：

green tea polyphenols; epigallocatechin-3-gallate; para-aminobenzoic acid; pro-drug; proteasome; apoptosis;

D O I：

10.1016/j.bmc.2007.05.041

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-NH2 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. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：5076 / 5082

页数：7

共 39 条

[1] The development of proteasome inhibitors as anticancer drugs [J].

Adams, J .

CANCER CELL, 2004, 5 (05) :417-421

[2] Novel dipeptidyl proteasome inhibitors overcome Bcl-2 protective function and selectively accumulate the cyclin-dependent kinase inhibitor p27 and induce apoptosis in transformed, but not normal, human fibroblasts [J].

An, B ;

Goldfarb, RH ;

Siman, R ;

Dou, QP .

CELL DEATH AND DIFFERENTIATION, 1998, 5 (12) :1062-1075

[3]

An B, 1996, CANCER RES, V56, P438

[4] Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: A preliminary report from a one-year proof-of-principle study [J].

Bettuzzi, S ;

Brausi, M ;

Rizzi, F ;

Castagnetti, G ;

Peracchia, G ;

Corti, A .

CANCER RESEARCH, 2006, 66 (02) :1234-1240

[5] Degradation of green tea catechins in tea drinks [J].

Chen, ZY ;

Zhu, QY ;

Tsang, D ;

Huang, Y .

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2001, 49 (01) :477-482

[6]

Ciechanover A, 2000, BIOESSAYS, V22, P442, DOI 10.1002/(SICI)1521-1878(200005)22:5<442::AID-BIES6>3.0.CO

[7]

2-Q

[8] Two stages of cancer prevention with green tea [J].

Fujiki, H .

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 1999, 125 (11) :589-597

[9] Cancer Prevention with Green Tea Polyphenols for the General Population, and for Patients Following Cancer Treatment [J].

Fujiki, Hirota ;

Suganuma, Masami ;

Matsuyama, Satoru ;

Miyazaki, Kohji .

CURRENT CANCER THERAPY REVIEWS, 2005, 1 (01) :109-114

[10] Structure of 20S proteasome from yeast at 2.4 angstrom resolution [J].

Groll, M ;

Ditzel, L ;

Lowe, J ;

Stock, D ;

Bochtler, M ;

Bartunik, HD ;

Huber, R .

NATURE, 1997, 386 (6624) :463-471

← 1 2 3 4 →