Amsacrine analogues with extended chromophores: DNA binding and anti-tumour activity

A series of phenanthroline analogues of the 9-anilinoacridine anti-leukaemic drug amsacrine were prepared and evaluated, with the aim of providing more weakly-basic derivatives which retained high levels of DNA binding. All the phenanthroline derivatives were stronger DNA-binding ligands than the corresponding acridine compounds, and the 1,7- and 1,8-phenanthrolines were weaker bases by 2 pKa units. The 1,10-phenanthroline derivative showed superior in vivo activity against the P388 leukaemia and the Lewis lung solid tumour than the corresponding acridine derivative amsacrine, but the other phenanthroline compounds did not have improved activity.