Design, synthesis, and biological evaluation of substituted naphtalene imides and diimides as anticancer agents

The search for novel chemotherapeutic agents and approaches to cancer treatment is an active research field stimulated by the discovery of new biological targets and by the possibility of obtaining new drugs without serious and undesirable side effects. Small molecules able to reversibly interact with the DNA structure represent a prolific research area for new potential anticancer agents. Such molecules, known as intercalators, are typically characterized by a planar heterocyclic moiety of approximately the size and shape of a DNA base pair. In the literature, there are several examples of naphthalimmide (NI) and 1,4,5,8- naphtalentetracaboxylic diimide (NDI) derivatives as intercalating agents [1]. Two important prototypes of these series are represented by N-DMPrNI and N-BDMPrNDI [2], which showed the ability to intercalate into steps containing at least one G:C base pair. These considerations prompted us to design derivatives using NI and NDI scaffolds as molecular building blocks. These new NI and NDI derivatives contain one or two basic polymethylene chains, respectively, in their structures, whose length may have relevance for the anticancer activity.