New spiro tria(thia)zolidine-acridines as topoisomerase inhibitors, DNA binders and cytostatic compounds
Abstrakt
tThree new diphenylsubstituted spirotriazolidine- and thiazolidinone-acridines were prepared and theirinteraction with calf thymus DNA investigated with UV-vis, fluorescence, circular dichroism spectroscopyand viscometry. The binding constants K were estimated to range from 0.34 to 0.93 x 104M -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.
Thebiological activity of compounds 3, 5 & 6 at several different concentrations (10, 20 and 50 M) wasevaluated both 48 h and 72 h following their addition to HL-60 cancer cells. The results were analysedusing various different techniques (MMP detection, changes in metabolic activity/viability and analysisof cell cycle distribution).
Acridine was also used as the positive control in these assays. The results fromMMP 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 6were less effective than derivative 5 and the acridine control.