Taming unconventional nucleic acid structures: synthesis of acridine- and 1,10-phenanthroline-based G-quadruplex...

In the past 30 years acridine and 1,10-phenanthroline ring systems have become more widespread in the investigation of novel G-quadruplex binding compounds. Starting from the well-known BRACO19 and PhenDC3 these biologically active scaffolds have undergone several major structural changes to improve the affinity and selectivity of these noncanonical DNA and RNA structures. The library of these molecules is dominated by symmetrical derivatives, however recently asymmetrical analogues have also found their way to be the focus of several research groups. Furthermore, the modification of the 1,10-phenanthroline ring system has also been investigated and has led to derivatives with competent G-quadruplex binding capabilities. The aim of this review is to provide a comprehensive look into the chemistry behind these molecules and to investigate the most widely used methods to achieve these compounds.