DNA Intercalation by Quinacrine and Methylene Blue: A Comparative Binding and Thermodynamic Characterization Study

Abstract

There is compelling evidence that cellular DNA is the target of many anticancer agents. Consequently, elucidation of the molecular nature governing the interaction of small molecules to DNA is paramount to the progression of rational drug design strategies. In this study, we have compared the binding and thermodynamic aspects of two known DNA-binding agents, quinacrine (QNA) and methylene blue (MB), with calf thymus (CT) DNA. The study revealed noncooperative binding phenomena for both the drugs to DNA with an affinity one order higher for QNA compared to MB as observed from diverse techniques, but both bindings obeyed neighbor exclusion principle. The data of the salt dependence of QNA and MB from the plot of log K versus log [Na+] revealed a slope of 1.06 and 0.93 consistent with the values predicted by theories for the binding of monovalent cations, and have been analyzed for contributions from polyelectrolytic and nonpolyelectrolytic forces. The binding of both drugs was further characterized by strong stabilization of DNA against thermal strand separation in both optical melting and differential scanning calorimetry studies. The binding data analyzed from the thermal denaturation and from isothermal titration calorimetry (ITC) were in close proximity to those obtained from spectral titration data. ITC results revealed the binding to be exothermic and favored by both negative enthalpy and positive entropy changes. The heat capacity changes obtained from temperature dependence of enthalpy indicated -146 and -78 cal/(mol.K), respectively, for the binding of QNA and MB to CT DNA. Circular dichroism study further characterized the structural changes on DNA upon intercalation of these molecules. Molecular aspects of interaction of these molecules to DNA are discussed.

Biophysical studies on the base specificity and energetics of the DNA interaction of photoactive dye thionine: Spectroscopic and calorimetric approach

“…The free energy contribution from the hydrophobic transfer step of binding of these molecules may be calculated from the relationship [50], ΔG hyd =80(±10) × ΔCp. The ΔG hyd values for thionine binding to CP, HT and ML DNAs were deduced to be −8.1, −10.7 and −16.7 kcal/mol, that are well within the range that was observed for typical intercalating DNA and RNA intercalating molecules [21,24,36,42,44,48,51].…”

Sequence Specific Binding of Beta Carboline Alkaloid Harmalol with Deoxyribonucleotides: Binding Heterogeneity, Conformational, Thermodynamic and Cytotoxic Aspects

“…7A,B). Though, Δ G hyd o value for harmalol binding to poly(dA-dT).poly(dA-dT) is slightly lower, but with poly(dG-dC).poly(dG-dC), the value was well within the range that was observed for classical intercalators [51], [54], [56]. Thus these results clearly indicate the involvement of a remarkably large hydrophobic contribution in harmalol-polynucleotide interaction.…”

Synthesis and in vitro antiproliferative activity of 5-alkyl-12(H)-quino[3,4-b] [1,4]benzothiazinium salts

“…It might be supposed then that these compounds would share a similar mode of antiproliferative action. This mode of action affecting cancer cells' DNA has been indeed suggested in reports concerning antiproliferative properties of phenothiazine and benzo [a]phenothiazine derivatives [6,22,23]. Structurally, compounds (3) studied herein are their analogs.…”