Interaction Of Calf Thymus DNA Research Articles

A new insight into the interaction of ZnO with calf thymus DNA through surface defects

Experimental evidences on the binding interaction of ZnO and Calf Thymus (CT) DNA using several biophysical techniques are the centre of interest of the present study. The interaction of ZnO with CT DNA has been investigated in detail by absorption spectral study, fluorescence titration, Raman analysis, zeta potential measurement, viscometric experiment along with thermal melting study and microscopic analysis. Steady-state fluorescence study revealed the quenching (48%) of the surface defect related peak intensity of ZnO on interaction with DNA. The optimized concentration of ZnO and DNA to obtain this level of quenching has been found to be 0.049mM and 1.027μM, respectively. Additional fluorescence study with 8-hydroxy-5-quinoline (HQ) as a fluorescence probe for Zn2+ ruled out the dissolution effect of ZnO under the experimental conditions. DNA conjugation on the surface of ZnO was also supported by Raman study. The quantitative variation in conductivity as well as electrophoretic mobility indicated significant interaction of ZnO with the DNA molecule. Circular dichroism (CD) and viscometry titrations provided clear evidence in support of the conformational retention of the DNA on interaction with ZnO. The binding interaction was found to be predominantly entropy driven in nature. The bio-physical studies presented in this paper exploring ZnO-CT DNA interaction could add a new horizon to understand the interaction between metal oxide and DNA.

Multi-analytical studies about physico-chemical properties of Ni(II)-vitamin B6 coordination compounds and their CT-DNA interactions

Two coordination compounds and their structural characterization of [Ni(PM)2]Cl2 and [Ni(PL)2]Cl2 have been studied. Pyridoxamine (PM) and pyridoxal (PL) denote individual vitamers of vitamin B6 and both demonstrated bidentate nature inside the complexes. The acid-base behavior of the mentioned complexes and their possible interactions with biomolecules in solutions have been never reported. Here, UV-spectroscopic, potentiometric, cyclic voltammetric studies have been carried out on the interaction of the Ni(II)-vitamer complexes with protons as well as with calf thymus-DNA (CT-DNA) in aqueous medium. The acidity constants values of coordination compounds studied have been determined and compared. The potentiometric and pHmetric-spectrophotometric microtitrations were carried out at the same conditions of temperature and pH range, 25°C and 1.72–11.68, respectively. The procedural decomposition temperatures of the complexes were given and considered in relation to the structures of the examined compounds to complete the structural description of [Ni(PM)2]Cl2 and [Ni(PL)2]Cl2. The CT-DNA binding potential of Ni(II) complexes was carried out by absorption spectroscopy and cyclic voltammetry methods. Mechanism investigation has demonstrated that examined compounds could interact to CT-DNA by grooving binding mode, which was stabilized by hydrogen bond and van der Waals forces.

Spectroscopic and molecular docking studies on the interaction of antiviral drug nevirapine with calf thymus DNA

ABSTRACTThe interaction of calf thymus DNA with nevirapine at physiological pH was studied by using absorption, circular dichroism, viscosity, differential pulse voltammetry, fluorescence techniques, salt effect studies and computational methods. The drug binds to ct-DNA in a groove binding mode, as shown by slight variation in the viscosity of ct-DNA. Furthermore, competitive fluorimetric studies with Hoechst 33258 indicate that nevirapine binds to DNA via groove binding. Moreover, the structure of nevirapine was optimized by DFT calculations and was used for the molecular docking calculations. The molecular docking results suggested that nevirapine prefers to bind on the minor groove of ct-DNA.

G-quadruplex and calf thymus DNA interaction of quaternized tetra and octa pyridyloxy substituted indium (III) phthalocyanines

The interactions of small molecules with G-quadruplex and double stranded DNA are important due to their potential biological and medical usages. In the present paper, the interactions of indium (III) phthalocyanines (quaternized 2,3,9,10,16,17,23,24-octakis-[(3-pyridyloxy) phthalocyaninato] chloroindium(III): OInPc and quaternized 2(3),9(10),16(17),23(24)-tetrakis-[(3-pyridyloxy) phthalocyaninato] chloroindium(III): TInPc) with hybrid G-quadruplex (Tel 21) and parallel G-quadruplexes (nucleolin, KRAS, c-MYC, vegf) were studied. The interactions of these phthalocyanines with ctDNA were also investigated. These interactions were measured by different spectroscopic techniques such as UV–Vis, fluorescence and circular dichroism. The UV–Vis spectroscopic data treated with Benesi-Hildebrand equation and Benesi-Hildebrand constants (KBH) were calculated. These constants were found higher for octa peripheral pyridyloxy substituted phthalocyanine, OInPc. Besides, UV–Vis analysis showed that the interaction of G-quadruplexes with tetra peripheral pyridyloxy substituted phthalocyanine derivative (TInPc) resulted in removal of central indium (III) atom from the cavity of phthalocyanine macrocycle. The UV–Vis melting studies as well as fluorescence replacement techniques were also employed for clarification of mechanism. The binding mode of molecules with ct DNA was also supported with viscosity measurements. From the results, the stabilization and destabilization of G-quadruplex depending on the concentration of the OInPc and TInPc showed that these two indium (III) phthalocyanines have the potential of both the elucidation role of G-quadruplexes in gene expression and the usage in cancer therapy.

Interaction of phenylethanoid glycosides and calf thymus DNA

In physiological condition, the interaction of acteoside and forsythoside B with calf thymus DNA using neutral red (NR) as a fluorescence probe were investigated by fluorescence, UV-visible spectrophotometry, viscosity, DNA melting techniques, and molecular docking. It is observed that acteoside and forsythoside B can react with DNA. The major mode of recognition between drug and DNA is groove binding by hydrogen bonds, and the interaction of acteoside with DNA is stronger than that of forsythoside B.

Synthesis, crystal structure, biomolecular interactions and anticancer properties of Ni(II), Cu(II) and Zn(II) complexes bearing S-allyldithiocarbazate

A new series of bivalent Ni(II), Cu(II) and Zn(II) metal complexes containing Schiff base ligand [H-emk-sadtc] [(E)-allyl 2-(butan-2-ylidene) hydrazine carbodithioate)] were synthesized and characterized by different spectroscopic techniques. The molecular structure of the ligand and its complexes 1 [(E)-allyl 2-(butan-2-ylidene) hydrazine carbodithioato nickel(II)], complex 2 [(E)-allyl 2-(butan-2-ylidene) hydrazine carbodithioato copper(II)], complex 3 [(E)-allyl 2-(butan-2-ylidene) hydrazine carbodithioato zinc(II)] were confirmed by single crystal X-ray crystallography. XRD data of the complexes had revealed a distorted square planar geometry around the metal ion, satisfied by N2S2 fashion. Density functional calculations of all the compounds in gas phase were performed by using DFT (B3LYP) with 6-311G basis set. The calculated FT-IR and structural data are in good agreement with the experimental results and confirmed by the experimental one. The interactions of calf thymus (CT) DNA and bovine serum albumin (BSA) with complexes 1–3 were explored by emission spectra. Catecholase and phosphatase-like activities of all the complexes were also investigated. An in vitro cytotoxicity study of the complexes had shown significant activity against human cervical cancer cell line (HeLa) with the best results of complex 2, which was found to be more toxic to cancer cells with a few micromolar concentrations, as the IC50 value, but significantly less toxic to normal cell lines. Additionally, the cell death analysis was carried out by AO/EB and DAPI staining methods.

Synthesis and characterization of pharmacologically active 18-membered tetraamide macrocyclic complexes of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II): In vitro antimicrobial, anticancer screening, DNA interaction and docking studies

ABSTRACTThe macrocyclic ligand, 2, 4: 11, 13-Dinaphthyl-1, 5, 10, 14 tetraazacyclooctadecane-6, 9, 15, 18-tetraone, (L) obtained from condensation of 1, 8-diaminonaphthalene and succinic acid, was used to synthesize the complexes of the type, [MLCl2] [M = Mn(II), Co(II), Ni(II), Cu(II) and Zn(II)] and characterized by spectroscopic techniques. The calf-thymus DNA interaction and CD studies indicated relatively greater binding ability for Cu(II) complex via groove binding. The in vitro cytotoxicity toward the cell line HeLa and MCF-7 has been evaluated by MTT assay. Therefore, Cu(II) complex seems as a superlative candidate offering a probable alternative to traditional chemotherapeutic agents.

Scrutinizing the DNA damaging and antimicrobial abilities of triazole appended metal complexes

New mononuclear transition metal complexes 1–12 bearing the bioactive triazole analogues were synthesized and characterized by elemental analysis and spectroscopic techniques. The interaction of calf thymus DNA (CT-DNA) with the synthesized compounds was studied at physiological pH by spectrophotometric, spectrofluorometric, cyclic voltammetry, and viscometric techniques. The entire DNA binding results suggested the intercalative mode of binding for the synthesized compounds. Interestingly, the binding strength of the complexes is found to be greater than that of the free ligands. Among the complexes explored, complex 5 reveals strong hypochromism and a slight red shift as compared to the other complexes highlighting its higher DNA binding propensity. The intrinsic binding constant values of the complexes compared to cisplatin reveal that all the complexes are greater in magnitude than that of cisplatin. Fluorescence titrations show that the Cu(II) complexes have the ability to displace DNA-bound ethidium bromide. Also, these compounds induce cleavage in pBR322 plasmid DNA as indicated in gel electrophoresis and exhibit excellent nuclease activity in the presence of H2O2. Moreover, the complexes were screened for in vitro antimicrobial activity along with free ligands and solvent control. The outcome is that the complexes possess good activity than the free ligands. These complexes may have further scope in developing them into antimicrobial drugs and DNA probes.

Synthesis, DNA-binding properties and cytotoxicity evaluation of two copper(II) complexes based on curcumin

Two Cu(II) complexes based on curcumin, namely CuL 2 1 [HL1 = 1,7-bis[4-(2-oxymethylenepyridine)-3-methoxyl]phenyl-1,6-heptadiene-3,5-diketone] and CuL 2 2 [HL2 = 1,7-bis[4-(3-oxymethylene-2-chlorothiophene)-3-methoxyl] phenyl-1,6-heptadiene-3,5-diketone], have been synthesized and characterized by physico-chemical and spectroscopic methods. The interactions of calf thymus DNA (CT-DNA) with both complexes have been investigated by UV–Vis absorption, fluorescence and viscosity titration methods. Both complexes are found to interact with CT-DNA by intercalative binding modes. Evaluation of the cytotoxicities of the complexes against three human tumor cells showed that they have potent cytotoxicities against all three cell lines.

Analytical approaches for clarification of DNA-double decker phthalocyanine binding mechanism: As an alternative anticancer chemotherapeutic

In the present study a novel water soluble double-decker phthalocyanine was synthesized and calf thymus DNA interaction of the synthesized double-decker phthalocyanine was investigated. 5-(3-pyridyl)-1,3,4-oxadiazole substituted phthalonitrile 1 was prepared by a nucleophilic displacement reaction of 4-nitrophthalonitrile with 5-(3-pyridyl)-1,3,4-oxadiazole-2-thiol. Lutetium(III) double-decker phthalocyanine 2 was prepared by cyclotetramerization of compound 1. Water soluble lutetium(III) double-decker phthalocyanine 3 was prepared with quaternarization of compound 2. The synthesized double-decker phthalocyanine and calf thymus DNA interaction was investigated with UV–vis titrimetric methods, gel electrophoresis, and viscosity measurements. The fluorometric ethidium bromide replacement assay was conducted to clarify the binding mode of water soluble double-decker phthalocyanine. The thermodynamic parameters for interaction, K, ΔG0, ΔH0 and ΔS0 were calculated between the temperature ranges of 25°C–75°C. To the best of our knowledge, this is the first study about a double-decker phthalocyanine and DNA interaction.

Investigation on the Binding Mode of 3, 4-Dihydropyrano[c]Chromene Derivative with Double Strand DNA.

The study on the interaction between small molecules and DNA has been very useful for investigating the structure and physical properties of DNA, elucidating the damage mechanism of DNA and significant in the design of new drugs targeted to DNA. This article describes an interaction of native calf thymus DNA (ctDNA) with a new 3, 4-dihydropyrano[c]chromene derivative, 2-amino-4-(4- chlorophenyl)-5-oxo-4H, 5H-pyrano-[3, 2-c] chromene-3-carbonitrile (4-CC) by using spectroscopic and viscometric techniques. The interaction between 4-CC and ctDNA is realized from the UV absorption spectrophotometry, viscosimetry, circular dichroism and fluorescence spectroscopic techniques which shows that the successive interaction of 4-CC with ctDNA occurs. The experimental results revealed that 4-CC can interact with DNA through non- intercalative mode and the intrinsic binding constant (Kb) for 4-CC with DNA was estimated to 2.37 (±0.001) ×103 M-1. Methylene blue (MB) displacement studies revealed that 4-CC did not have any effect on MB bound DNA which is indicative of groove binding mode. Furthermore, 4-CC induces detectable changes in the CD spectrum of ctDNA as well as changes in its viscosity study corroborate the above experimental results. These results further advance our knowledge on the molecular aspects on the interaction of 4-CC to nucleic acids.

Thermodynamics of interaction and structure of DNA complexes with phenacylimidazo[5,1-a]isoquinoline derivatives

Interaction of native calf thymus DNA (ctDNA) with phenacylimidazo[5,1- a]isoquinoline derivatives was studied by the methods of spectrophotometry, viscometry, isothermal titration calorimetry (ITC) and dynamic birefringence. It was found that both of investigated compounds form complexes with the DNA molecule, the structure of compounds affects the mode of binding these ligands to DNA. The primary binding mode can not be described by the classical models of groove binding or intercalation. It has been suggested that the primary mode of binding is "partial intercalation".

Spectral, electrochemical, and molecular docking evaluation of the interaction of the anti-hyperthyroid drug methimazole with DNA

The interaction of native calf thymus DNA with the anti-hyperthyroid drug methimazole was investigated by different spectroscopic (UV-Vis spectrophotometry, spectroflourimetry, and circular dichroism), electrochemical (cyclic voltammetry and chronoamperometry) methods, and molecular docking calculations. The binding constant (Kb) obtained from the spectrophotometric method was 9.67 × 103 L mol−1, comparable with that of groove binding molecules. The binding mode was further investigated by following the competition between Hoechst 33258 and methimazole for DNA grooves by spectrofluorimetry. Consistent results were obtained from all experimental methods used in this study. Finally, theoretical calculations using the molecular docking method confirmed the experimental results.

Characterization of interaction of calf thymus DNA with gefitinib: Spectroscopic methods and molecular docking

The binding interaction of gefitinib with calf thymus DNA (ct-DNA) under the simulated physiological pH condition was studied employing UV absorption, fluorescence, circular dichroism (CD), viscosity measurement and molecular docking methods. The experimental results revealed that gefitinib preferred to bind to the minor groove of ct-DNA with the binding constant (Kb) of 1.29×104Lmol−1 at 298K. Base on the signs and magnitudes of the enthalpy change (ΔH0=−60.4kJmol−1) and entropy change (ΔS0=−124.7Jmol−1K−1) in the binding process and the results of molecular docking, it can be concluded that the main interaction forces between gefitinib and ct-DNA in the binding process were van der Waals force and hydrogen bonding interaction. The results of CD experiments revealed that gefitinib did not disturb native B-conformation of ct-DNA. And, the significant change in the conformation of gefitinib in gefitinib–ct-DNA complex was observed from the molecular docking results and the change was close relation with the structure of B-DNA fragments, indicating that the flexibility of gefitinib molecule also plays an important role in the formation of the stable gefitinib–ct-DNA complex.

Interaction studies between biosynthesized silver nanoparticle with calf thymus DNA and cytotoxicity of silver nanoparticles

The interaction of calf thymus DNA (CTDNA) with silver nanoparticles (SNP) has been investigated following spectroscopic studies, analysis of melting temperature (Tm) curves and hydrodynamic measurement. In spectrophotometric titration and thermal denaturation studies of CTDNA it was found that SNP can form a complex with double-helical DNA and the increasing value of Tm also supported the same. The association constant of SNP with DNA from UV–Vis study was found to be 4.1×103L/mol. The fluorescence emission spectra of intercalated ethidium bromide (EB) with increasing concentration of SNP represented a significant reduction of EB intensity and quenching of EB fluorescence. The results of circular dichroism (CD) suggested that SNP can change the conformation of DNA. From spectroscopic, hydrodynamic, and DNA melting studies, SNP has been found to be a DNA groove binder possessing partial intercalating property. Cell cytotoxicity of SNP was compared with that of normal silver salt solution on HeLa cells. Our results show that SNP has less cytotoxicity compared to its normal salt solution and good cell staining property.

Formation of intermolecular crosslinks by the actinocin derivatives with DNA in interaction under conditions of semidilute solution

Interaction of native calf thymus DNA (ctDNA) with the actinocin derivatives containing protonated diethylamino groups, dimethylamino groups and unsubstituted amino groups and having different length of the alkyl chain have been studied by the method of viscometry. An anomalous hydrodynamic behavior of solutions of DNA with very low amount of ligands prepared under conditions of semidilute solution was revealed. We assumed that such an anomalous behavior of solutions of DNA complexes with actinocin derivatives associated with the formation of intermolecular crosslinks while the preparation of the complex was in terms of overlapping of macromolecular coils in solution. Comparative study of the hydrodynamic behavior of the DNA complexes with various actinocin structures lead us to the conclusion of the formation of crosslinks by the compounds containing protonated diethylamino groups.

Spectroscopic and viscositic studies on the interaction of solifenacin succinate with DNA

The interaction of native calf thymus DNA (ctDNA) with solifenacin succinate (SFS) was investigated under simulated physiological conditions by multi-spectroscopic techniques and viscometric measurements. It concluded that SFS could intercalate into the base pairs of ctDNA, and the fluorescence quenching by ctDNA was static quenching type. Thermodynamic parameters calculated suggested that the binding of SFS to ctDNA was mainly driven by hydrophobic interactions. Furthermore, the relative viscosity of ctDNA increased with the addition of SFS, which confirmed the intercalation mode.

Phenyl carbohydrazone conjugated 2-oxoindoline as a new scaffold that augments the DNA and BSA binding affinity and anti-proliferative activity of a 1,10-phenanthroline based copper(II) complex

A new type of copper(II) complex, [CuL(phen)2](NO3) (CuIP), where L ((E)-N′-(2-oxoindolin-3-ylidene)benzohydrazide) is a N donor ligand and phen is the N, N-donor heterocyclic 1,10-phenanthroline, has been synthesized. The phenyl carbohydrazone conjugated isatin-based ligand L and CuIP were characterized by elemental analysis, infrared, UV–Vis, 1H and 13C NMR and ESI-mass spectral data, as well as single-crystal X-ray diffraction. The interaction of calf thymus DNA (CT DNA) with L and CuIP has been investigated by absorption, fluorescence and viscosity titration methods. The complex CuIP displays better binding affinity than the ligand L. The observed DNA binding constant (Kb=4.15(±0.18)×105M−1) and binding site size (s=0.19), viscosity data together with molecular docking studies of CuIP suggest groove binding and/or a partial intercalative mode of binding to CT DNA. In addition, CuIP shows good binding propensity to the bovine serum albumin (BSA) protein, giving a KBSA value of 1.25(±0.24)×106M−1. In addition, the docking studies on DNA and human serum albumin (HSA) CuIP interactions are consistent with the consequence of binding experiments. The in vitro anti-proliferative study establishes the anticancer potency of the CuIP against the human cervical (HeLa) and breast (MCF7) cancer cells; noncancer breast epithelial (MCF10a) cells have also been investigated. CuIP shows better cytotoxicity and sensitivity towards cancer cells over noncancer ones than L under identical conditions, with the appearance of apoptotic bodies.

Conformational changes of DNA in the presence of 12-s-12 gemini surfactants (s = 2 and 10). Role of the spacer's length in the interaction surfactant-polynucleotide

A multifaceted study on the interaction of calf-thymus DNA with two different cationic gemini surfactants alkanediyl-α-ω-bis(dodecyldimethyl-amonium)bromide, 12-s-12,2Br− (with s=2, G2, and 10, G10) was carried out. The measurements were done at different molar ratios X=[surfactant]/[DNA]. Results show two different conformational changes in DNA: a first compaction of the polynucleotide corresponding to a partial conformational (not total) change of DNA from an extended coil state to a globular state that happens at the lower molar ratio X. A second change corresponds to a breaking of the partial condensation, that is, the transition from the compacted state to a new more extended conformation (for the higher X values) different to the initial extension. According to circular dichroism spectra and dynamic light scattering measurements, this new state of DNA seems to be similar to a ψ-phase. Measurements confirm that interactions involved in the compaction are different to those previously obtained for the analog surfactant CTAB. X values at which the conformational changes happen depend on the length of the spacer in the surfactant along with the charge of the polar heads.

X-ray crystal structure of a Cu(II) complex with the antiparasitic drug tinidazole, interaction with calf thymus DNA and evidence for antibacterial activity

Interaction of metal ions with biologically active molecules like 5-nitroimidazoles modulates their electronic environment and therefore influences their biological function. In the present work, an antiparasitic drug tinidazole (tnz) was selected and a Cu(II) complex of tnz [Cu2(OAc)4(tnz)2] was prepared. A dinuclear paddle-wheel [Cu2(OAc)4(tnz)2] was obtained by single-crystal XRD and further characterized by spectroscopic techniques and cyclic voltammetry. To understand the biological implications of complex formation, interaction of tnz and its complex was studied with calf thymus DNA, bacterial and fungal cell lines. Results of calf thymus DNA interaction using cyclic voltammetry indicate the overall binding constant (K*) of Cu2(OAc)4(tnz)2 [(59 ± 6) × 104 M−1] is ~17 times greater than that of tnz [(3.3 ± 0.4) × 104 M−1]. Minimum inhibitory concentration values suggest that [Cu2(OAc)4(tnz)2] possesses better antibacterial activity than tnz on both bacterial strains, while the activity on a fungal strain was comparable.