Isatin derivatives, a novel class of transthyretin fibrillogenesis inhibitors

Asensio González; Josefina Quirante; Joan Nieto; Maria Rosário Almeida; Maria Joao Saraiva; Antoni Planas; Gemma Arsequell; Gregorio Valencia

doi:10.1016/j.bmcl.2009.03.004

Isatin derivatives, a novel class of transthyretin fibrillogenesis inhibitors

Asensio González, Josefina Quirante, Joan Nieto, Maria Rosário Almeida, Maria Joao Saraiva, Antoni Planas, Gemma Arsequell, Gregorio Valencia

Producció científica: Article en revista indexada › Article › Avaluat per experts

48 Cites (Scopus)

Resum

The isatin core structure was found to be a novel chemical scaffold in transthyretin (TTR) fibrillogenesis inhibitor design. Among the series of isatin analogues prepared and tested, the nitro compound 1,3-dihydro-3-[(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 ¹H 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.

Idioma original	Anglès
Pàgines (de-a)	5270-5273
Nombre de pàgines	4
Revista	Bioorganic and Medicinal Chemistry Letters
Volum	19
Número	17
DOIs	https://doi.org/10.1016/j.bmcl.2009.03.004
Estat de la publicació	Publicada - 1 de set. 2009

Accés al document

10.1016/j.bmcl.2009.03.004

Altres arxius i enllaços

Com citar-ho

@article{ce4a8325a67e4966b3b3f67948eff9a5,

title = "Isatin derivatives, a novel class of transthyretin fibrillogenesis inhibitors",

abstract = "The isatin core structure was found to be a novel chemical scaffold in transthyretin (TTR) fibrillogenesis inhibitor design. Among the series of isatin analogues prepared and tested, the nitro compound 1,3-dihydro-3-[(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 1H 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.",

keywords = "Amyloidosis, Inhibitors, Isatins, Transthyretin",

author = "Asensio Gonz{\'a}lez and Josefina Quirante and Joan Nieto and Almeida, {Maria Ros{\'a}rio} and Saraiva, {Maria Joao} and Antoni Planas and Gemma Arsequell and Gregorio Valencia",

note = "Funding Information: This work was financially supported by grants to projects POCI/SAU-MMO/57321/2004 from FCT-Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia (Portugal) and CTQ2006-02390/BQU and BIO2007-67904-C02-02 from Ministerio de Ciencia y Tecnologia (Spain). ",

year = "2009",

month = sep,

day = "1",

doi = "10.1016/j.bmcl.2009.03.004",

language = "English",

volume = "19",

pages = "5270--5273",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd.",

number = "17",

}

TY - JOUR

T1 - Isatin derivatives, a novel class of transthyretin fibrillogenesis inhibitors

AU - González, Asensio

AU - Quirante, Josefina

AU - Nieto, Joan

AU - Almeida, Maria Rosário

AU - Saraiva, Maria Joao

AU - Planas, Antoni

AU - Arsequell, Gemma

AU - Valencia, Gregorio

N1 - Funding Information: This work was financially supported by grants to projects POCI/SAU-MMO/57321/2004 from FCT-Fundação para a Ciência e Tecnologia (Portugal) and CTQ2006-02390/BQU and BIO2007-67904-C02-02 from Ministerio de Ciencia y Tecnologia (Spain).

PY - 2009/9/1

Y1 - 2009/9/1

N2 - The isatin core structure was found to be a novel chemical scaffold in transthyretin (TTR) fibrillogenesis inhibitor design. Among the series of isatin analogues prepared and tested, the nitro compound 1,3-dihydro-3-[(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 1H 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.

AB - The isatin core structure was found to be a novel chemical scaffold in transthyretin (TTR) fibrillogenesis inhibitor design. Among the series of isatin analogues prepared and tested, the nitro compound 1,3-dihydro-3-[(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 1H 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.

KW - Amyloidosis

KW - Inhibitors

KW - Isatins

KW - Transthyretin

UR - http://www.scopus.com/inward/record.url?scp=68549085257&partnerID=8YFLogxK

UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000268863800085&DestLinkType=FullRecord&DestApp=WOS_CPL

U2 - 10.1016/j.bmcl.2009.03.004

DO - 10.1016/j.bmcl.2009.03.004

M3 - Article

C2 - 19651509

AN - SCOPUS:68549085257

SN - 0960-894X

VL - 19

SP - 5270

EP - 5273

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 17

ER -

Isatin derivatives, a novel class of transthyretin fibrillogenesis inhibitors

Resum

Accés al document

Altres arxius i enllaços

Fingerprint

Com citar-ho