New spiro tria(thia)zolidine-acridines as topoisomerase inhibitors, DNA binders and cytostatic compounds
Othman M. Salem, Mária Vilková, Jana Janočková, Rastislav Jendželovský, Peter Fedoročko, Eva Žilecká, Jana Kašpárková, Viktor Brabec, Ján Imrich, Mária Kožurková
International Journal of Biological Macromolecules
Three new diphenylsubstituted spirotriazolidine- and thiazolidinone–acridines were prepared and their interaction with calf thymus DNA investigated with UV–vis, fluorescence, circular dichroism spectroscopy and viscometry. The binding constants Kwere estimated to range from 0.34 to 0.93 × 104 M−1. UV–vis, fluorescence and circular dichroism measurements indicated that the compounds act as effective DNA-interacting agents. Electrophoretic separation proved that ligands inhibited topoisomerase I and II. The biological activity of compounds 3, 5 & 6 at several different concentrations (10, 20 and 50 μM) was evaluated both 48 h and 72 h following their addition to HL-60 cancer cells. The results were analysed using various different techniques (MMP detection, changes in metabolic activity/viability and analysis of cell cycle distribution). Acridine was also used as the positive control in these assays. The results from MMP analysis demonstrate the strong effect of 3-diphenylamino-2-(acridin-9-yl)imino-1,3-thiazolidin-4-one (5) on mitochondrial physiology. Cell viability analysis showed that acridine derivatives 3 and 6 were less effective than derivative 5 and the acridine control.
Circular dichroism, Ligand binding, Biochemistry