Isatin derivatives, a novel class of transthyretin fibrillogenesis inhibitors

被引：39

作者：

Gonzalez, Asensio ^{[2
]}

Quirante, Josefina ^{[2
]}

Nieto, Joan ^{[3
]}

Almeida, Maria Rosario ^{[4
,5
]}

Saraiva, Maria Joao ^{[4
,5
]}

Planas, Antoni ^{[3
]}

Arsequell, Gemma ^{[1
]}

Valencia, Gregorio ^{[1
]}

机构：

[1] CSIC, IQAC, Barcelona, Spain

[2] Univ Barcelona, Fac Farm, Lab Quim Organ, Inst Biomed, E-08028 Barcelona, Spain

[3] Univ Ramon Llull, Inst Quim Sarria, Dept Bioengn, Biochem Lab, Barcelona, Spain

[4] Univ Porto, IBMC, Mol Neurobiol Unit, Oporto, Portugal

[5] Univ Porto, Dept Biol Mol, ICBAS, Oporto, Portugal

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 17期

关键词：

Isatins; Transthyretin; Amyloidosis; Inhibitors; IN-VITRO; ANTILEUKEMIC ACTIVITY; STABILIZATION; CYTOTOXICITY; DISEASES; RECEPTOR; SU11248; ANALOGS; POTENT;

D O I：

10.1016/j.bmcl.2009.03.004

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The isatin core structure was found to be a novel chemical scaffold in transthyretin (TTR) brillogenesis inhibitor design. Among the series of isatin analogues prepared and tested, the nitro compound 1,3-dihydro3-[(4-nitrophenyl)imino]-2H-indol-2-one (2r) is as potent as triiodophenol, which is one of the most active known TTR inhibitors. The E/Z stereochemistry of these molecules in solution, elucidated by H-1 NMR, does not influence their biological activity. The compounds do not bind to the native tetrameric TTR suggesting that their inhibitory action is independent of the protein binding and stabilization. (C) 2009 Published by Elsevier Ltd.

引用

页码：5270 / 5273

页数：4

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