Biochimie et physiologie : accès libre

Abstrait

Spectroscopic Studies of the Bis-3,6-Alkylamidoacridines as Potential Topoisomerase I Inhibitors

Danica Sabolová, Júlia Kudlácová, Ladislav Janovec and Ján Imrich

In this paper, the interaction of bis-3,6-alkylamidoacridines with calf thymus DNA (ctDNA) and their inhibitory effect on topoisomerase I are investigated. The binding mode of the low-molecular ligands to ctDNA was determined using UVvis absorption spectrophotometry, fluorescence spectrophotometry and circular dichroism. The binding constants for the DNA-drug complexes were estimated to be from 2.10×105 to 0.68×105 M-1, and the percentage of hypochromism was found to be over 25% (from UV-vis titrations). The effect of the investigated compounds on the transition temperature of ctDNA was detected using thermal denaturation studies. Experiments using arose gel electrophoresis demonstrated that the tested derivatives have an inhibitory effect on topoisomerase I.