Denny W A, Baguley B C
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
Anticancer Drug Des. 1987 Aug;2(1):61-70.
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.
制备并评估了9-苯胺基吖啶抗白血病药物安吖啶的一系列菲咯啉类似物，目的是提供碱性更弱但仍保持高水平DNA结合能力的衍生物。所有菲咯啉衍生物都是比相应吖啶化合物更强的DNA结合配体，且1,7-和1,8-菲咯啉的碱性比相应吖啶弱2个pKa单位。1,10-菲咯啉衍生物对P388白血病和Lewis肺癌实体瘤的体内活性优于相应的吖啶衍生物安吖啶，但其他菲咯啉化合物的活性并未提高。
