Simplified aminocoumarin analogues as anticancer agents: Amino isosteric replacement in the noviose moiety resulted in substantial enhancement of antiproliferative activity

Simplified aminocoumarin analogues, either noviosylated or simple basic heterocycle attached 3-amido-coumarin compounds, are known to be promising anticancer agents targeting the C-terminal ATP-binding site of Hsp90. In this study, 3′-amino isosteric replacement in the noviose moiety of two known noviose containing Hsp90 C-terminal inhibitors was synthetically realized for the first time. In vitro evaluation of these compounds suggested that the introduction of a basic amino group into the noviose subunit resulted in significant improvement of their cytotoxicities.

Graphical abstractA novel series of simplified aminocoumarin analogues with the 3′-NH2 isosteric replacement in the noviose appendage were synthesized and evaluated.Figure optionsDownload full-size imageDownload as PowerPoint slide