Easy access to Ugi-derived Isatin-peptoids and their potential as small-molecule anticancer agents

Abstract

An amide bond is one of the most important functional motifs in chemistry and biology due to its presence in countless biological structures and is of significant synthetic interest. Small-molecule amides are remarkable scaffolds for designing new drugs. Here, we report a new Ugi4CR approach using 5-amino-3,3-protected-oxindole derivatives, carboxylic acids (and nitrophenols), aldehydes (and ketones) and isocyanides to create a library of Ugi-derived isatin-peptoids in moderate to excellent yields, in a one-step, clean, and fast sustainable reaction process. The library was tested against human solid tumor cell lines. The results allowed some preliminary structure–activity relationships to be established. The most active derivative showed GI50 values in the range of 0.06–2.3 μM.