Novel CADD-based peptidyl vinyl ester derivatives as potential proteasome inhibitors

被引：18

作者：

Mou, Ke ^{[1
]}

Xu, Bo ^{[1
]}

Ma, Chao ^{[1
]}

Yang, Xiaoming ^{[1
]}

Zou, Xiaomin ^{[1
]}

Lue, Yang ^{[1
]}

Xu, Ping ^{[1
]}

机构：

[1] Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Dept Med Chem, Beijing 100083, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 06期

关键词：

binding mode; CADD; synthesis; bioactivity; proteasome inhibitor; peptidomimetic; peptidyl vinyl ester derivatives;

D O I：

10.1016/j.bmcl.2007.12.077

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of peptidyl vinyl ester derivatives bearing three different P1 substitutions as potential proteasome inhibitors were studied. The target molecules were designed based on CADD (computer aided drug design) protocol and synthesized. Their activities toward proteasome and four human cancer cell lines (including hepatoma cell line (Bel-7402), myeloid leukemic cell line (HL-60), gastric cancer cell line (BGC-823) and nasopharyngeal cancer cell line (KB)) were tested using fluorescence assay. Two compounds showed proteasome inhibitory activities, and four compounds showed weak antiproliferative activities toward HL-60 and BGC-823. (C) 2008 Elsevier Ltd. All rights reserved.

引用

收藏

页码：2198 / 2202

页数：5

相关论文

共 28 条

[1] The proteasome: A suitable antineoplastic target [J].

Adams, J .

NATURE REVIEWS CANCER, 2004, 4 (05) :349-360

[2] Potent and selective inhibitors of the proteasome: Dipeptidyl boronic acids [J].

Adams, J ;

Behnke, M ;

Chen, SW ;

Cruickshank, AA ;

Dick, LR ;

Grenier, L ;

Klunder, JM ;

Ma, YT ;

Plamondon, L ;

Stein, RL .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (04) :333-338

[3] P′-extended α-ketoamide inhibitors of proteasome [J].

Chattejee, S ;

Dunn, D ;

Mallya, S ;

Ator, MA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (17) :2603-2606

[4] Autocatalytic subunit processing couples active site formation in the 20S proteasome to completion of assembly [J].

Chen, P ;

Hochstrasser, M .

CELL, 1996, 86 (06) :961-972

[5] THE UBIQUITIN-PROTEASOME PROTEOLYTIC PATHWAY [J].

CIECHANOVER, A .

CELL, 1994, 79 (01) :13-21

[6] Towards subunit-specific proteasome inhibitors:: synthesis and evaluation of peptide α′,β′-epoxyketones [J].

Elofsson, M ;

Splittgerber, U ;

Myung, J ;

Mohan, R ;

Crews, CM .

CHEMISTRY & BIOLOGY, 1999, 6 (11) :811-822

[7] Modeling of the binding mode of a non-covalent inhibitor of the 20S proteasome.: Application to structure-based analogue design [J].

Furet, P ;

Imbach, P ;

Fürst, P ;

Lang, M ;

Noorani, M ;

Zimmermann, J ;

Garcia-Echeverría, C .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (10) :1321-1324

[8] A new structural class of selective and non-covalent inhibitors of the chymotrypsin-like activity of the 20S proteasome [J].

Garcia-Echeverría, C ;

Imbach, P ;

France, D ;

Fürst, P ;

Lang, M ;

Noorani, M ;

Scholz, D ;

Zimmermann, J ;

Furet, P .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (10) :1317-1319

[9] Crystal structure of epoxomicin:20S proteasome reveals a molecular basis for selectivity of α′,β′-epoxyketone proteasome inhibitors [J].

Groll, M ;

Kim, KB ;

Kairies, N ;

Huber, R ;

Crews, CM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (06) :1237-1238

[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