Synthesis and antiproliferative activity of some variously substituted acridine and azacridine derivatives

A group of 9-substituted acridine and azacridine derivatives (m-AMSA analog ues) were synthesised following classical procedures as potential antitumou r agents with inhibitory effects on DNA topoisomerase II. Some were found t o have noticeable cytotoxicity against human HL-60 and HeLa cells grown in culture. Their non-covalent interactions with calf thymus DNA have been stu died using fluorescence quenching. We evaluated DNA damage produced by the tested compounds by means of DNA filter elution and protein precipitation t echniques. Catalytic studies carried out with purified topoisomerase confir med these agents as antitopoisomerase inhibitors. Chemotherapy of solid-tum our-bearing mice with tested compounds allowed an aza-analogue (compound II Ib), as potent as m-AMSA but less toxic towards the host, to be recognised. (C) 2000 Editions scientifiques et medicales Elsevier SAS.