DNA intercalation by quinacrine and methylene blue: a comparative binding and thermodynamic characterization study.

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.

[1]  G. S. Kumar,et al.  Molecular aspects on the interaction of protoberberine, benzophenanthridine, and aristolochia group of alkaloids with nucleic acid structures and biological perspectives , 2007, Medicinal research reviews.

[2]  G. S. Kumar,et al.  Molecular recognition of DNA by small molecules: AT base pair specific intercalative binding of cytotoxic plant alkaloid palmatine. , 2007, Biochimica et biophysica acta.

[3]  L. Cronin,et al.  Microcalorimetry of interaction of dihydro-imidazo-phenanthridinium (DIP)-based compounds with duplex DNA. , 2007, Biophysical chemistry.

[4]  Ali Akbar Saboury,et al.  Stability and structural features of DNA intercalation with ethidium bromide, acridine orange and methylene blue , 2007 .

[5]  G. S. Kumar,et al.  RNA binding small molecules: studies on t-RNA binding by cytotoxic plant alkaloids berberine, palmatine and the comparison to ethidium. , 2007, Biophysical chemistry.

[6]  G. S. Kumar,et al.  Protoberberine Alkaloids: Physicochemical and Nucleic Acid Binding Properties , 2007 .

[7]  Karen L. Buchmueller,et al.  Physical and structural basis for the strong interactions of the -ImPy- central pairing motif in the polyamide f-ImPyIm. , 2006, Biochemistry.

[8]  Y. Liang,et al.  Applications of isothermal titration calorimetry in protein folding and molecular recognition , 2006, Journal of the Iranian Chemical Society.

[9]  A. Saboury.  A review on the ligand binding studies by isothermal titration calorimetry , 2006 .

[10]  Binh Nguyen,et al.  Binding-linked protonation of a DNA minor-groove agent. , 2006, Biophysical journal.

[11]  G. S. Kumar,et al.  Protonated structures of naturally occurring deoxyribonucleic acids and their interaction with berberine. , 2005, Bioorganic & medicinal chemistry.

[12]  R. O'brien,et al.  Applications of Biocalorimetry: Binding, Stability and Enzyme Kinetics , 2005 .

[13]  Xue Zhang,et al.  Inactivation of dengue virus by methylene blue/narrow bandwidth light system , 2004, Journal of Photochemistry and Photobiology B: Biology.

[14]  M. Aslanoglu,et al.  Voltammetric studies of the interaction of quinacrine with DNA , 2004, Analytical and bioanalytical chemistry.

[15]  G. Tang,et al.  The binding properties of photosensitizer methylene blue to herring sperm DNA: a spectroscopic study. , 2004, Journal of photochemistry and photobiology. B, Biology.

[16]  G. S. Kumar,et al.  Protonated forms of poly[d(G-C)] and poly(dG).poly(dC) and their interaction with berberine. , 2003, Bioorganic & medicinal chemistry.

[17]  I. Haq.  Thermodynamics of drug-DNA interactions. , 2002, Archives of biochemistry and biophysics.

[18]  Laurence H. Hurley,et al.  DNA and its associated processes as targets for cancer therapy , 2002, Nature Reviews Cancer.

[19]  M. Devynck,et al.  Quinacrine increases endothelial nitric oxide release: role of superoxide anion. , 2002, European journal of pharmacology.

[20]  L. Hurley,et al.  Secondary DNA structures as molecular targets for cancer therapeutics. , 2001, Biochemical Society transactions.

[21]  P. Dervan,et al.  Molecular recognition of DNA by small molecules. , 2001, Bioorganic & medicinal chemistry.

[22]  T. Gardner,et al.  Treatment of Giardiasis , 2001, Clinical Microbiology Reviews.

[23]  K. Stuhlmeier.  Effects of quinacrine on endothelial cell morphology and transcription factor-DNA interactions. , 2000, Biochimica et biophysica acta.

[24]  S. Sánchez‐Cortés,et al.  Interaction of Antimalarial Drug Quinacrine with Nucleic Acids of Variable Sequence Studied by Spectroscopic Methods , 2000, Journal of biomolecular structure & dynamics.

[25]  J. Chaires,et al.  Energetics of DNA intercalation reactions. , 2000, Biochemistry.

[26]  A. Moor,et al.  Photodynamic treatment of pooled coumarin plasma for external quality assessment of the prothrombin time , 2000, Journal of clinical pathology.

[27]  F. Murphy,et al.  Nonsequence-specific DNA recognition: a structural perspective. , 2000, Structure.

[28]  J. Chaires.  Drug--DNA interactions. , 1998, Current opinion in structural biology.

[29]  J. Chaires,et al.  Energetics of drug-DNA interactions. , 1997, Biopolymers.

[30]  J. Chaires.  Dissecting the free energy of drug binding to DNA. , 1996, Anti-cancer drug design.

[31]  J. Chaires,et al.  Parsing the free energy of anthracycline antibiotic binding to DNA. , 1996, Biochemistry.

[32]  B. Nordén,et al.  Sequence-Specific Interactions of Methylene Blue with Polynucleotides and DNA: A Spectroscopic Study , 1994 .

[33]  R. Shafer,et al.  Differential binding of the enantiomers of chloroquine and quinacrine to polynucleotides: Implications for stereoselective metabolism , 1993, Biopolymers.

[34]  J. Ha,et al.  Role of the hydrophobic effect in stability of site-specific protein-DNA complexes. , 1989, Journal of molecular biology.

[35]  B. Nordén,et al.  Induced CD of DNA intercalators: Electric dipole allowed transitions , 1987, Biopolymers.

[36]  G. S. Manning,et al.  Polyelectrolyte effects on site‐binding equilibria with application to the intercalation of drugs into DNA , 1984, Biopolymers.

[37]  F. Chen.  Pyrene as a sensitive probe for DNA conformational changes due to protonation. , 1983, Journal of biomolecular structure & dynamics.

[38]  G. Baldini,et al.  Thermodynamics of the intercalation of acridines in DNA , 1982 .

[39]  B. Nordén,et al.  Structure of methylene blue–DNA complexes studied by linear and circular dichroism spectroscopy , 1982, Biopolymers.

[40]  D. Crothers,et al.  Studies on interaction of anthracycline antibiotics and deoxyribonucleic acid: equilibrium binding studies on interaction of daunomycin with deoxyribonucleic acid. , 1982, Biochemistry.

[41]  M. Waring,et al.  DNA modification and cancer. , 1981, Annual review of biochemistry.

[42]  W. Wilson,et al.  Analysis of cooperativity and ion effects in the interaction of quinacrine with DNA , 1979, Biopolymers.

[43]  T. Lohman,et al.  Thermodynamic analysis of ion effects on the binding and conformational equilibria of proteins and nucleic acids: the roles of ion association or release, screening, and ion effects on water activity , 1978, Quarterly Reviews of Biophysics.

[44]  D. Crothers,et al.  Interactions of heteroaromatic compounds with nucleic acids. 1. The influence of heteroatoms and polarizability on the base specificity of intercalating ligands. , 1975, European journal of biochemistry.

[45]  P. V. von Hippel,et al.  Theoretical aspects of DNA-protein interactions: co-operative and non-co-operative binding of large ligands to a one-dimensional homogeneous lattice. , 1974, Journal of molecular biology.

[46]  D. Crothers.  Statistical thermodynamics of nucleic acid melting transitions with coupled binding equilibria , 1971, Biopolymers.

[47]  J. Ciak,et al.  Quinacrine (Atebrin): Mode of Action , 1967, Science.