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 (1)H 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.
authors: Laboratori de Química Orgànica, Facultat de Farmàcia, Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Spain.
authors: Asensio
authors: A
authors: González
authors: Josefina
authors: J
authors: Quirante
authors: Joan
authors: J
authors: Nieto
authors: Maria Rosário
authors: MR
authors: Almeida
authors: Maria Joao
authors: MJ
authors: Saraiva
authors: Antoni
authors: A
authors: Planas
authors: Gemma
authors: G
authors: Arsequell
authors: Gregorio
authors: G
authors: Valencia
mesh_terms: D015195:Drug Design; D007510:Isatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011228:Prealbumin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D011228:Prealbumin; D007510:Isatin