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

Article Details

Citation

Ferlin MG, Marzano C, Chiarelotto G, Baccichetti F, Bordin F

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

Eur J Med Chem. 2000 Sep;35(9):827-37.

PubMed ID
11006484 [ View in PubMed
]
Abstract

A group of 9-substituted acridine and azacridine derivatives (m-AMSA analogues) were synthesised following classical procedures as potential antitumour agents with inhibitory effects on DNA topoisomerase II. Some were found to have noticeable cytotoxicity against human HL-60 and HeLa cells grown in culture. Their non-covalent interactions with calf thymus DNA have been studied using fluorescence quenching. We evaluated DNA damage produced by the tested compounds by means of DNA filter elution and protein precipitation techniques. Catalytic studies carried out with purified topoisomerase confirmed these agents as antitopoisomerase inhibitors. Chemotherapy of solid-tumour-bearing mice with tested compounds allowed an aza-analogue (compound IIIb), as potent as m-AMSA but less toxic towards the host, to be recognised.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AmsacrineDNA topoisomerase 2-alphaProteinHumans
Yes
Inhibitor
Details