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 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.

Graphical abstractThe isatin core structure was found to be a novel chemical scaffold in transthyretin (TTR) fibrillogenesis inhibitor design.Figure optionsDownload full-size imageDownload as PowerPoint slide