Design, synthesis and biological evaluation of new naphtalene diimides bearing isothiocyanate functionality

The synthesis and the biological activities of new derivatives 1–3, characterized by the isothiocyanate (ITC) functionalities coming from sulforaphane (SFN), a well-known anticancer natural product, were reported. The most interesting compound of the series was 2. It was chemically characterized by two ITC functionalities mounted on the 1,4,5,8-naphthalentetracarboxylic diimide (NDI) scaffold through two polymethylene chains, each constituted by three carbon units. It demonstrated an IC50 value in the submicromolar range, more potent than SFN, displaying also the ability to trigger apoptotic induction in the same range by eliciting both extrinsic and intrinsic apoptotic pathways. Finally, it was observed that 2 inhibited the cell growth by blocking the cell cycle in G1 phase.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The dimethylamino groups of N-BDMPrNDI were substituted with isothiocyanate functionalities. ► The new derivatives showed the ability to inhibit cell growth in the submicromolar range. ► Compound 2 triggered the apoptotic induction in the micromolar range. ► Compound 2 decreased the mitochondrial potential in the same range. ► The new derivatives blocked the cell cycle in G1 phase.