Abstrakt
This research was focused on a study of the binding properties of a series of cholinesterase reactiva-tors compounds K075 (1), K027 (2) and inhibitors compounds K524, K009 and 7-MEOTA (3–5) with calfthymus DNA. The nature of the interactions between compounds 1–5 and DNA were studied using spec-troscopic techniques (UV–vis, fluorescence spectroscopy and circular dichroism).
The binding constantsfor complexes of cholinesterase modulators with DNA were determined from UV–vis spectroscopic titra-tions (K = 0.5 × 104–8.9 × 105M−1). The ability of the prepared analogues to relax topoisomerase I wasstudied with electrophoretic techniques and it was proved that ligands 4 and 5 inhibited this enzymeat a concentration of 30 M.
The biological activity of the novel compounds was assessed through anexamination of changes in cell cycle distribution, mitochondrial membrane potential and cellular via-bility. Inhibitors 3–5 exhibited a cytotoxic effect on HL-60 (human acute promyelocytic leukaemia) cellculture, demonstrated a tendency to affect mitochondrial physiology and viability, and also forced cellsto accumulate in the G1/G0-phase of the cell cycle.
The cholinesterase reactivators 1 and 2 were foundrelatively save from the point of view of DNA binding, whereas cholinesterase inhibitors 3–5 resulted asstrong DNA binding agents that limit their plausible use.