Novel Polyamine–Naphthalene Diimide Conjugates Targeting Histone Deacetylases and DNA for Cancer Phenotype Reprogramming

Abstract

A series of hybrid compounds was designed to target histone deacetylases and ds-/G-quadruplex DNAs by merging structural features deriving from Scriptaid and compound <b>1</b>. Compound <b>6</b> binds different DNA arrangements, inhibits HDACs both <i>in vitro</i> and in cells, and is able to induce a reduction of cell proliferation. Moreover, compound <b>6</b> displays cell phenotype-reprogramming properties since it prevents the epithelial to mesenchymal transition in cancer cells, inducing a less aggressive and migratory phenotype, which is one of the goals of present innovative strategies in cancer therapies.