One-step template-directed synthesis of acridine-based rigid cyclophanes

Abstract

Cyclo-bisintercalands are macrocyclic systems containing aromatic subunits, which are commonly used as hosts for aromatic molecules and as DNA intercalators. In this article, a step-by-step synthesis of a series of cyclo-bisintercalands containing 3,6-diaminoacridines as aromatic units, and connected by rigid spacers of different lengths, is reported. In addition, we describe herein a more efficient synthetic alternative, involving single-step template-directed processes. The new routes allow the easy synthetic access to these macrocyclic systems with acceptable yields. The synthesized cyclo-bisintercalands and their precursors have been structurally characterized by UV–visible and NMR methods. Preliminary biological activity assays performed on the bisintercalands and cyclo bisintercalands revealed interesting cytotoxic properties against different tumor cell lines, especially in the case of the bisintercalands, highlighting their potential as cancer chemotherapeutic agents.