Spectroscopic and In Silico Evaluation of Interaction of DNA with Six Anthraquinone Derivatives (original) (raw)
Related papers
DNA-binding, DNA cleavage and cytotoxicity studies of two anthraquinone derivatives
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2012
The interaction of native calf thymus DNA (CT-DNA) with two anthraquinones including quinizarin (1,4-dihydroxy anthraquinone) and danthron (1,8-dihydroxy anthraquinone) in a mixture of 0.04 M Brittone-Robinson buffer and 50% of ethanol were studied at physiological pH by spectrofluorometric and cyclic voltammetry techniques. The former technique was used to calculate the binding constants of anthraquinones-DNA complexes at different temperatures. Thermodynamic study indicated that the reactions of both anthraquinone-DNA systems are predominantly entropically driven. Furthermore, the binding mechanisms on the reaction of the two anthraquinones with DNA and the effect of ionic strength on the fluorescence property of the system have also been investigated. The results of the experiments indicated that the binding modes of quinizarin and danthron with DNA were evaluated to be groove binding. Moreover, the cytotoxic activity of both compounds against human chronic myelogenous leukemia K562 cell line and DNA cleavage were investigated. The results indicated that these compounds slightly cleavage pUC18 plasmid DNA and showed minor antitumor activity against K562 (human chronic myeloid leukemia) cell line.
DNA-binding study of anthraquinone derivatives using Chemometrics methods
European Journal of Medicinal Chemistry, 2011
This work presents the interaction of two anthraquinones including quinizarin (1, 4-dihydroxyanthraquinone) and danthron (1, 8-dihydroxyanthraquinone) with CT-DNA in a mixture of Brittone eRobinson buffer (pH ¼ 7) with 50% of ethanol by UVevis absorption, circular dichroism spectroscopic methods and viscosity measurements. The PCA and INDICES methods were used for predicting the number of light-absorbing components. Partially intercalative and hydrogen binding were found to be the dominant binding modes between anthraquinones and CT-DNA. The effect of ionic strength and pH on the behavior of the above system and also the interaction of anthraquinones with ds and ss-DNA were used to confirm the mentioned binding modes. The EQUISPEC software and nonlinear least-squares analysis were applied for binding constant determination.
DNA TARGETED ANTHRAQUINONE DERIVATIVES: AN IMPORTANT ANTICANCER AGENTS
International Journal of Pharmacy and Pharmaceutical Sciences, 2016
Deoxyribonucleic acid, DNA is the source of various genetic information and is currently one of the most important and studied biological receptor. Lately, a wide range of chemotherapeutic agents are known wherein they affect cell division or DNA synthesis, leading to inhibition of cell growth and cell death. Out of various agents anthraquinone, having a planar tricyclic structure is the backbone of many known antitumor drugs like doxorubicin and mitoxantrone capable of targeting at the molecular/DNA level. This review embraces discussion on DNA-binding molecules with special attention to anthraquinone based compounds having application in anticancer activity by DNA damage mechanism. The review also compiles the work reported on anthraquinone based molecule in molecular imaging.
Journal of the Brazilian Chemical Society, 2009
Com base em nossa investigação, ambos os complexos, morin-Bi(III) e Morin, podem vincularse ao DNA, embora a natureza da ligação seja diferente para cada um deles. Na presença e ausência do DNA, o morin-Bi(III) mostrou características espectrais diferentes, o que está de acordo com as observadas para outros intercaladores. Neste trabalho, a interação do complexo morin-Bi(III) com o DNA de timo de vitela foi investigada com o uso do azul de metileno (MB), como uma sonda de corante espectral e aplicação de espectrofotometria UV-Vis, espectroscopia de fluorescência e voltametria cíclica. A proporção de 2:1 do complexo de morin-Bi(III) foi calculada pela espectroscopia UV-Vis (método da razão molar). Observou-se que o sinal de fluorescência do complexo Bi(III)-morin é aumentado com a adição de DNA enquanto que o sinal do morin é diminuído com adição de DNA. O sinal de fluorescência do complexo-DNA desaparece pela adição de MB, o que confirma o deslocamento do complexo com MB. Os estudos de voltametria cíclica confirmam a reação de intercalação. Os resultados mostraram que somente o complexo de morin-Bi(III) pode intercalar-se em dupla hélice com o DNA. A constante aparente do complexo morin-Bi(III) com o DNA é de 2.8 × 10 4 L mol-1 , enquanto que o morin liga-se por um modelo de não-intercalação. Based on our investigation, although both morin-Bi(III) complex and morin can bind to DNA, the nature of the binding was found to be different for each of them. In the presence and absence of the DNA, the morin-Bi(III) complex shows different spectral characteristics which agree with those observed for other intercalators. In this work, the interaction of morin-Bi(III) complex with calf thymus DNA was investigated with the use of methylene blue (MB) dye as a spectral probe and application of UV-Vis spectrophotometry, fluorescence spectroscopy and cyclic voltammetry. The 2:1 morin-Bi(III) complex ratio was calculated by UV-Vis spectroscopy (mole ratio method). The fluorescence signal of Bi(III)-morin complex is increased with DNA addition whereas the fluorescence signal of Morin is decreased with DNA addition. The fluorescence signal of the DNA-complex is quenched by addition of MB which confirms the displacement of the complex with MB. Cyclic voltammetry studies confirm the intercalation reaction. The results showed that only morin-Bi(III) complex can intercalate into the double helix of the DNA. The apparent binding constant of morin-Bi(III) complex with DNA is found to be 2.8 × 10 4 L mol-1 , while morin binds in a non-intercalation mode.
Molecular Therapy - Nucleic Acids
G-quadruplex is a non-canonical secondary structure identified in the telomeric region and the promoter of many oncogenes. Anthraquinone derivatives, a well-known inducer of telomere disruption in malignant cells and activate the apoptotic pathway. We used biophysical and biochemical studies to confirm the interaction of synthesized anthraquinone derivatives with the human telomeric G-quadruplex sequence. The binding affinity of N-2DEA and N-1DEA are K b = 4.8 Â 10 6 M À1 and K b = 7.6 Â 10 5 M À1 , respectively, leading to hypochroism, fluorescence quenching with minor redshift and ellipticity variations indicating ligand binding in the external groove. We found that sodium ions induced stabilization more rather than potassium ions. Molecular docking of complex demonstrates a molecule's exterior binding to a quadruplex. The investigation of ROS activity indicated that the cell initiates mortality in response to the IC 50 concentration. Cellular morphology, nuclear condensation, and fragmentation were altered in the treated cell, impairing cellular function. Finally, the transcriptional regulatory study paves the way for drug design as an anticancer agent because of the tremendous possibilities of changing substituent groups on anthraquinones to improve efficacy and selectivity for G-quartet DNA. Our research focused on how ligand binding to telomere sequences induces oxidative stress and inhibits the growth of malignant cells.
FEBS Letters, 1986
The interaction has been studied of several anthraquinone-based intercalating drugs, including the anti-cancer agent mitoxantrone, with defined sites of DNA. A 160 base pair DNA sequence from tyrT was employed for footprinting with DNase I. The anthraquinones had aminoalkylamino substituents in various positions of the ring system. Inhibition of enzymatic cutting of the DNA was observed at various positions on the sequence, mostly around some of the pyrimidine-3',5'-purine sites. Enhancements to cutting were observed clustered around AT-rich regions. The compounds showed differences in detailed footprinting behaviour, which have been related to differences in their mode of interaction with DNA as found in earlier computer modelling studies.
Journal of Physical Organic Chemistry, 2012
Hydroxy-9,10-anthraquinones resemble anthracycline-based anticancer drugs. By varying the pH of the solution, the proton dissociation constants of 1,2,5,8-tetrahydroxy-9,10-anthraquinone (THAQ) were determined. Interaction of THAQ with calf thymus DNA (ct DNA) was studied by UV-Vis spectroscopy to determine the overall binding constant and site size of interaction. The binding constant values (~10 4) for THAQ interacting with ct DNA at different pH were an order less than that known for anthracyclines. From knowledge of the overall binding constants at different pH values and the first pK of THAQ, the contribution of each form (neutral and monoanionic) towards overall binding with ct DNA could be obtained under physiological conditions. Hence, knowing the contributions of the neutral and monoanionic forms, it now becomes possible to know the overall binding constant for an interaction of THAQ with ct DNA at any pH. The calculated parameters help in understanding the role of the negative charge on the monoanionic form during interaction and suggests suitable chemical modifications that could prevent the development of such negative charges. This could lead to an increase in binding of THAQ to ct DNA. The study also helps to recognize the importance of sugar units in anthracycline anticancer drugs in DNA interaction.
Journal of Chemical Sciences, 2002
The interaction of 8-methoxypyrimido[4′,5′:4,5]thieno(2,3-b)quinoline-4(3H)one (MPTQ) with DNA was studied by UV-Vis and fluorescence spectrophotometry as well as by hydrodynamic methods. On binding to DNA, the absorption spectrum underwent bathochromic and hypochromic shifts and the fluorescence was quenched. Binding parameters, determined from spectrophotometric measurements by Scatchard analysis, indicated a binding constant of 3.56 × 10 6 M -1 for calf thymus DNA at ionic strength 0⋅01 M. Binding to the GC-rich DNA of Micrococcus lysodeikticus was stronger than the binding to calf thymus DNA at ionic strength 0⋅01 M. The MPTQ increased the viscosity of sonicated rod-like DNA fragments, producing a calculated length of 2⋅4 Å/bound MPTQ molecule. The binding of MPTQ to DNA increased the melting temperature by about 4°C. This research offers a new intercalation functional group to DNA targetted drug design.
Journal of photochemistry and photobiology. B, Biology, 2013
Mitoxantrone (MTX) (1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione) is a synthetic antineoplastic drug, widely used as a potent chemotherapeutic agent in the treatment of various types of cancer. It is structurally similar to classical anthracyclines. Widespread interest in the anticancer agent mitoxantrone has arisen because of its apparent lower risk of cardio-toxic effects compared to the naturally occurring anthracyclines. In the present work, we investigated the interaction of mitoxantrone with DNA in the buffer solution at physiological pH using Fourier transform infrared (FTIR), UV-Visible absorption and circular dichroism spectroscopic techniques. FTIR analysis revealed the intercalation of mitoxantrone between the DNA base pairs along with its external binding with phosphate-sugar backbone. The binding constant calculated for mitoxantrone-DNA association was found to be 3.88 Â 10 5 M À1 indicating high affinity of drug with DNA double helix. Circular dichroism spectroscopic results suggest that there are no major conformational changes in DNA upon interaction with drug except some perturbations in native B-DNA at local level. The present work shows the capability of spectroscopic analysis to characterize the nature of drug-biomolecule complex and the effects of such interaction on the structure of biomolecule.