Synthesis and evaluation of coumermycin A1 analogues that inhibit the Hsp90 protein folding machinery

被引：85

作者：

Burlison, Joseph A. ^{[1
]}

Blagg, Brian S. J. ^{[1
]}

机构：

[1] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA

来源：

ORGANIC LETTERS | 2006年 / 8卷 / 21期

关键词：

D O I：

10.1021/ol061918j

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

[GRAPHICS] The coumarin antibiotics are not only potent inhibitors of DNA gyrase but also represent the most effective C-terminal inhibitors of 90 kDa heat shock proteins (Hsp90) reported thus far. In contrast to the N-terminal ATP-binding site, little is known about the Hsp90 C-terminus. In addition, very limited structure-activity relationships exist between this class of natural products and Hsp90. In this letter, the syntheses of dimeric coumarin analogues are presented along with their inhibitory values in breast cancer cell lines.

引用

页码：4855 / 4858

页数：4

共 20 条

[1] Hsp90 inhibitors: Small molecules that transform the Hsp90 protein folding machinery into a catalyst for protein degradation [J].

Blagg, BSJ ;

Kerr, TA .

MEDICINAL RESEARCH REVIEWS, 2006, 26 (03) :310-338

[2] Hsp90: the vulnerable chaperone [J].

Chiosis, G ;

Vilenchik, M ;

Kim, J ;

Solit, D .

DRUG DISCOVERY TODAY, 2004, 9 (20) :881-888

[3] Design, synthesis, and evaluation of a radicicol and geldanamycin chimera, radamide [J].

Clevenger, RC ;

Blagg, BSJ .

ORGANIC LETTERS, 2004, 6 (24) :4459-4462

[4] Recent developments in olefin cross-metathesis [J].

Connon, SJ ;

Blechert, S .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (17) :1900-1923

[5] Binding of ATP to heat shock protein 90 - Evidence for an ATP-binding site in the C-terminal domain [J].

Garnier, C ;

Lafitte, D ;

Tsvetkov, PO ;

Barbier, P ;

Leclerc-Devin, J ;

Millot, JM ;

Briand, C ;

Makarov, AA ;

Catelli, MG ;

Peyrot, V .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (14) :12208-12214

[6] Synthesis of new artemisinin-derived dimers by self-cross-metathesis reaction [J].

Grellepois, F ;

Crousse, B ;

Bonnet-Delpon, D ;

Bégué, JP .

ORGANIC LETTERS, 2005, 7 (23) :5219-5222

[7] Microtiter cell-based assay for detection of agents that alter cellular levels of Her2 and EGFR [J].

Huezo, H ;

Vilenchik, M ;

Rosen, N ;

Chiosis, G .

CHEMISTRY & BIOLOGY, 2003, 10 (07) :629-634

[8] 2-BUTYNE-1-4-DIOL .1. REACTIONS OF THE HYDROXYL GROUPS [J].

JOHNSON, AW .

JOURNAL OF THE CHEMICAL SOCIETY, 1946, (NOV) :1009-1014

[9]

Kolb HC, 2001, ANGEW CHEM INT EDIT, V40, P2004, DOI 10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.3.CO

[10]

2-X

← 1 2 →