Isatin derivatives, a novel class of transthyretin fibrillogenesis inhibitors.
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.
González
Asensio
A
Laboratori de Química Orgànica, Facultat de Farmàcia, Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Spain.
Quirante
Josefina
J
Nieto
Joan
J
Almeida
Maria Rosário
MR
Saraiva
Maria Joao
MJ
Planas
Antoni
A
Arsequell
Gemma
G
Valencia
Gregorio
G
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
D011228:Prealbumin; D007510:Isatin