Groove Binding Mode Research Articles

Molecular mechanism of anionic stabilizer for telomere G-quadruplex.

Telomere DNA assumes a high-order G-quadruplex (G4) structure, stabilization of which prevents telomere lengthening by telomerase in cancer. Through applying combined molecular simulation methods, an investigation on the selective binding mechanism of anionic phthalocyanine 3,4',4'',4'''-tetrasulfonic acid (APC) and human hybrid (3 + 1) G4s was firstly performed at the atomic level. Compared to the groove binding mode of APC and the hybrid type I (hybrid-I) telomere G4, APC preferred to bind to the hybrid type II (hybrid-II) telomere G4 via end-stacking interactions, which showed much more favorable binding free energies. Analyses of the non-covalent interaction and binding free energy decomposition revealed a decisive role of van der Waals interaction in the binding of APC and telomere hybrid G4s. And the binding of APC and hybrid-II G4 that showed the highest binding affinity adopted the end-stacking binding mode to form the most extensive van der Waals interactions. These findings add new knowledge to the design of selective stabilizers targeting telomere G4 in cancer.

Synthesis of 4-((4-(4-nitrophenoxy)phenyl)diazenyl)benzene-1,3-benzoate:Experimental, DFT and, DNA binding investigation through spectral and molecular docking studies

Pharmacists and other researchers have always been fascinated by the DNA sensing evaluation. This piece of work emphasizes on the synthesis, characterization and DNA sensing of a novel azo ester (N = N, -COO) molecule. The product (1A) was synthesized employing a typical esterification reaction between previously reported resorcinol coupled azo dye and Benzoyl chloride. The structural interpretation of the synthesized ester was done by FT-IR (Fourier transform infrared), NMR (Nuclear magnetic resonance), UV/VIS (ultraviolet–visible spectroscopy), and single crystal X-ray diffraction studies. XRD analysis elucidated the Ester 1A to be in the Monoclinic system with P21/n space group. The DFT simulation experiments were also examined to investigate the structural implications of the resulting product. The higher softness (S), electrophilicity index (ω) and electronegativity (χ) values demonstrated greater polarizability and reactive nature of the compound. Further, wet and silico binding methods were employed to examine the DNA sensing ability of the synthesized molecule with SS-DNA. UV/VIS spectroscopy and hydrodynamic measurements (Viscosity) suggested Groove binding mode of interaction with a moderate value of binding constant, which was further confirmed by molecular docking techniques.

Synthesis, crystal structures and CT-DNA/BSA binding properties of Co(III) and Cu(II) complexes with bipyridine Schiff base ligand

A novel bipyridine Schiff base ligand C12H9ClN4O (HL) and its two transition metal complexes [CoL2]NO3⋅H2O (1) and CuL2⋅CH3OH (2) have been synthesized. Their structures have been characterized by single crystal XRD, showing that 1 and 2 belong to triclinic systems and P-1 space groups. TG-DTG results indicate that 1, 2 and HL all possess high thermal stabilities. The interactions of 1, 2 and HL with calf thymus DNA (CT-DNA) have been investigated by UV–vis spectra and fluorescence spectra, illustrating each complex binds to CT-DNA in an intercalation mode and HL interacted with CT-DNA through groove binding mode. Fluorescence spectroscopy has been used to determine the interactions of 1, 2 and HL with BSA, showing 1, 2 and HL can bind with BSA in static mechanism. Microcalorimetry measurements indicate that the processes of 1, 2 and HL interacting with CT-DNA and BSA are all exothermic, and the reactions complete within 35 min. The molecular docking shows that each compound binds to CT-DNA and BSA mainly through hydrophobic interactions and hydrogen bonds. In addition, 2 exhibits excellent antibacterial activities against Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis and Escherichia coli.

Key criteria for engineering mycotoxin binding aptamers via computational simulations: Aflatoxin B1 as a case study.

Due to the difficulties in monoclonal antibody production specific to mycotoxins, aptameric probes have been considered as suitable alternatives. The low efficiency of the SELEX procedure in screening high affinity aptamers for binding mycotoxins as small molecules can be significantly improved through computational techniques. Previously, we designed five new aptamers to aflatoxin B1 (AFB1) based on a known aptamer sequence (Patent: PCT/CA2010/001 292, Apt1) through a genetic algorithm-based in silico maturation strategy and experimentally measured their affinity to the target toxin. Here, integrated molecular dynamic simulation (MDs) studies with molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis to clarify the binding modes, critical interacting nucleic bases and energy component contributions in the six AFB1-binding aptamers. The aptamer F20, which was selected in the first work, showed the best free binding energy and complex stability compared to other aptamers. The trajectory analysis revealed that AFB1 recognized F20 through the groove binding mode along with precise shape complementarity. The MD simulation results revealed that dynamic water intermediate interactions also play a key role in promoting complex stability. According to the MM-PBSA calculations, van der Waals contacts were identified as dominant energy components in all complexes. Interestingly, a high consistency is observed between the experimentally obtained binding affinities of the six aptamers with their free energy solvation. The computational findings, confirmed via previous experiments, highlighted the binding modes, the dynamic hydration of complex components and the total free interacting energy as the crucial criteria in discovering high functional aptameric probes.

Nizatidine interacts with ct-DNA causing genotoxicity and cytotoxicity: an assessment by in vitro, in vivo, and in silico studies

H2 receptor antagonists are the medication given for treating stomach ulcers, but lately, reports have shown their role in healing several malignant ulcers. The present work entails the interaction of H2 blocker nizatidine with calf thymus (ct)-DNA for determining the binding mode and energetics of the interaction. Multi-spectroscopic, calorimetric, viscometric and bioinformatic analysis revealed that nizatidine interacted with ct-DNA via groove-binding mode and is characterised by exothermic reaction. Moreover, assessment of genotoxic potential of nizatidine in vitro was carried out in peripheral human lymphocytes by alkaline comet assay. DNA damage occurred at high concentrations of nizatidine. Genotoxicity of nizatidine was also evaluated in vivo by assessing cytogenetic biomarkers viz. micronuclei formation and chromosomal aberration test. Nizatidine was able to induce micronuclei formation and chromosomal damage at high dose. Additionally, cytotoxic activity of nizatidine was determined in cancer cell lines, namely HeLa and HCT-116 and compared with the normal human cell line HEK-293 employing MTT assay. It was observed that nizatidine was more toxic towards HeLa and HCT-116 than HEK-293. Cell morphology analysis by compound inverted microscopy further strengthens the finding obtained through MTT assay.

Modulating the chemo-mechanical response of structured DNA assemblies through binding molecules.

Recent advances in DNA nanotechnology led the fabrication and utilization of various DNA assemblies, but the development of a method to control their global shapes and mechanical flexibilities with high efficiency and repeatability is one of the remaining challenges for the realization of the molecular machines with on-demand functionalities. DNA-binding molecules with intercalation and groove binding modes are known to induce the perturbation on the geometrical and mechanical characteristics of DNA at the strand level, which might be effective in structured DNA assemblies as well. Here, we demonstrate that the chemo-mechanical response of DNA strands with binding ligands can change the global shape and stiffness of DNA origami nanostructures, thereby enabling the systematic modulation of them by selecting a proper ligand and its concentration. Multiple DNA-binding drugs and fluorophores were applied to straight and curved DNA origami bundles, which demonstrated a fast, recoverable, and controllable alteration of the bending persistence length and the radius of curvature of DNA nanostructures. This chemo-mechanical modulation of DNA nanostructures would provide a powerful tool for reconfigurable and dynamic actuation of DNA machineries.

Effect of ancillary ligand on DNA and protein interaction of the two Zn (II) and Co (III) complexes: experimental and theoretical study

In the present work we have developed one mononuclear Zn(II) complex [Zn(L)(H2O)] (Complex 1) by utilizing a tetracoordinated ligand H2L, formed by simple condensation of 2, 2 dimethyl 1,3 diamino propane and 3- ethoxy salicylaldehyde and one newly designed mononuclear Co (III) complex [Co(L)(L1)] (complex 2) by utilizing (H2L) and 3- ethoxy salicylaldehyde(HL1) as an ancillary ligand. The newly developed complex 2 have been spectroscopically characterized. An interesting phenomenon has been noticed that in presence of ancillary ligand, the solubility in buffer solution and the thermal stability of complex 2 comparatively increases than 1. To check the effect of ancillary ligand, present in complex 2 towards the DNA and HSA binding efficacy, both the complexes have been taken into consideration to inspect their binding potentiality with the macromolecules. The ‘on’, ‘off’ fluorescence changes in presence of DNA and HSA, the binding constant values, obtained from electronic spectral titration, iodide induced quenching, competitive binding assay, circular dichroism (CD) spectral titration, time resolved fluorescence experiment unambiguously assure the better binding efficacy of complex 2 with the signal of minor groove binding mode with DNA along with no significant conformational changes of the macromolecules. The strong and spontaneous binding of complex 2 with CT-DNA is further supported by the Isothermal Titration Calorimetry (ITC) study. Furthermore TDDFT calculation of DNA with and without complex 2 significantly authorize the formation of complex 2-DNA adduct during the association. Finally Molecular Docking study properly verifies the experimental findings and provides justified explanation behinds experimental findings.

A Cu(I) complex groove binder with a high affinity towards DNA denaturation

The interaction of ligands with double-stranded DNA is important for many intracellular processes. We demonstrate the ability of a copper(I) bis-triphenylphosphine based complex with a high affinity for target DNA via a minor groove binding mode. The fluorescence and UV–visible results show that a complex-DNA conjugate forms in the ground state with a binding affinity in order of 10+5 M−1. According to the findings of competitive fluorescence experiments, the phosphine substituent attaches in the minor groove of DNA by replacing Hoechst molecules at A-T rich regions. Also, relatively small changes in the CD spectrum of DNA as well as in its viscosity indicated that the Cu(I) complex could interact as a groove binder. The resulted entropy and enthalpy changes denoting the Van der Waals forces as the key binding mechanism in the interaction. Fluorescent DNA melting analysis shows that the Cu(I) complex is strongly disturbed the stability of the DNA base pairs, making the dsDNA to ssDNA easier to transition. The insertion of phosphine bulky substituents in the DNA minor groove was approved by docking analysis. Moreover, the molecular dynamic simulation shows an opening of DNA chains due to the Cu(I) complex force applied.

Crystal structures and study of interaction mode of bis-benzimidazole-benzene derivatives with DNA

Three derivatives of the scaffold, 1,3-bis(benzimidazol-2-yl)benzene 1–3, were synthesized and structurally characterized by single X-ray diffraction. Spectroscopic studies by fluorescence competitive displacement assays, UV–Vis, circular dichroism, and docking simulations revealed that the interaction of these derivatives with ds-DNA at pH= 7.4 is through groove binding mode with pronounced affinity to derivative 1 which contains hydrogen bond donor groups (NH), 1 (KA= 4.48 × 104 M−1), over the other derivatives lacking hydrogen bond donors, 2–3 (KA= 6.6 × 103 - 2.1 × 103 M−1). Melting DNA studies and Stern-Volmer constants at different temperatures of 1 with DNA are consistent with a static quenching mechanism by a groove binding mode. Based on experimentally estimated enthalpic (ΔH= -55.33 kJmol−1) and entropic (ΔS= -98.77 Jmol−1K−1) parameters, and theoretical calculations for the complex 1-DNA, the proposed interaction model is predominantly enthalpically driven through hydrogen bonds and Van der Waals.Finally, bisbenzimidazole derivatives 1 and 2 exhibit potential anti-proliferative activity toward human colorectal adenocarcinoma and human lung adenocarcinoma, respectively.

Deciphering the DNA-binding affinity, cytotoxicity and apoptosis induce as the anticancer mechanism of Bavachinin: An experimental and computational investigation

One of the most important mechanism by which bioflavonoids can exert their effects in cancer treatment, is through their interaction with bio-macromolecules such as DNA. Recent literature emphasizes the role of Bavachinin (BVC) as an emerging anticancer agent. However, there are no reports on its ability to interact with DNA. The present study investigated the DNA binding properties of BVC by many spectroscopic and computational approaches. The evidences are provided from UV–visible and CD spectral analyses illustrated that BVC interacted with ctDNA through minor groove binding mode. Based on the thermodynamic analyses, it can be inferred that the binding process was spontaneous, and the hydrophobic interaction played a major role in BVC-ctDNA binding. In silico molecular docking and dynamic simulation finally strengthened our experimental results that BVC was located in the minor groove (AT- rich) region of B-DNA structure and resulted in the slight alteration in the secondary structure of DNA during the interaction process. Additionally, BVC indicated significant cytotoxicity against MCF-7 breast cancer cells. Furthermore, quantitative analyses demonstrate that BVC treatment significantly increased the expression of pro-apoptotic genes; p53, caspase-3, -8, and -9 in MCF-7 cells. In order to further investigate the molecular targets of BVC, molecular docking studies indicated a relatively good binding affinity of BVC with pro-apoptotic proteins. In effect, BVC can be considered as a small organic compound with DNA binding property, appropriate cytotoxic activity, and potential of apoptotic inducing that can be adopted for medical science and pharmacy.

Design, synthesis, ligand’s scaffold variation and structure elucidation of Cu(II) complexes; In vitro DNA binding, morphological studies and their anticancer activity

Two new copper(II) complexes, Cu[(L)2(X)] (1) and Cu[(L)(X)2] (2) where L = 1,10-phenanthroline and X = (2-pyrimidylthio)-acetic acid (PTAA), have been synthesized and characterized utilizing physico-chemical techniques and single X-ray crystallography. Various techniques, like absorption, emission and CD spectroscopy, CV and SEM, were applied to explore drug-DNA interactions and their collaborative results revealed an electrostatic or groove binding mode of interaction of both drug candidates with ct-DNA. In addition, pBR322 cleavage activities were carried out which suggested significant oxidative cleavage with complex 1 compared to complex 2. Moreover, in vitro cytotoxic studies of complexes 1 and 2 were performed by an SRB assay against MCF-7, MDA-MB-231 and Hop-62 cancer cell lines. Both complexes showed good cytotoxic activity against all the cancer cell lines, with GI50 values < 10 μM. Interestingly, complex 1 exhibited a more efficient cytotoxic activity against MDA-MB-231 and HOP-62, even greater than that of the standard drug Adriamycin. Additionally, molecular docking studies were carried out which gave results that are in good agreement with the spectroscopic results. Furthermore, DFT calculations were performed and electrostatic maps were generated to shed light on the stability, charge density and reactivity of these complexes.

Quantitative fluorescent determination of DNA – Ochratoxin a interactions supported by nitrogen-vacancy rich nanodiamonds

Ochratoxin A (OTA) is a hazardous contaminant of a large variety of plant and animal originated food. Herein, we report an interaction of OTA with calf thymus DNA (ct DNA) on the nanodiamond surface. We employed multispectroscopic techniques to elucidate the binding mechanism of OTA with ct DNA. The fluorescence and UV–Vis spectroscopy results show that OTA binds to ds ct DNA and forms complexes.We obtained the binding constants of OTA and ct DNA using fluorescence quenching and UV–Vis spectroscopy. The binding constant (Kb) for the interaction of OTA with ct DNA was determined using spectroscopic methods and was determined as 3.27 × 105 M−1 (UV–Vis) and 8.12 × 105 M−1 (fluorescence) for nanodiamond in green tea beverage OTA. Performed analyses directly indicate that OTA can interact with calf thymus DNA in a groove-binding mode as proved by the hyperchromic effect of the absorption spectra. This study of OTA–ct DNA interaction may provide novel insights into the toxicological effect of the mycotoxins.

New imino-methoxy derivatives: design, synthesis, characterization, antimicrobial activity, DNA interaction and molecular docking studies

Four new diarylmethylamine imine compounds (5a-5d) were prepared in order to examine their DNA binding properties, antimicrobial activity and molecular docking. The compounds were characterized by the common spectroscopic and analytic methods. Furthermore, solid-state structure of compounds 5a and 5c were determined by single-crystal X-ray diffraction studies. The compounds were then investigated for their DNA binding properties employing UV absorption, fluorescence spectroscopy under the physiological pH condition Tris-HCl buffer at pH 7.4. The compounds 5a-5d showed moderate binding constants with Kb values of 3.56 ± 0.3 × 104, 2.18 ± 0.2 × 105, 1.44 ± 0.3 × 105 and 2.56 ± 0.3 × 104 M−1, respectively. The molecular dockings were performed to investigate the ligand-DNA interactions. The in-silico DNA-compound interaction studies showed that the compounds interact with DNA in groove binding mode. Antimicrobial activity studies of imine compounds were tested against E. coli as bacteria, S. typhimurium, S. aureus, B. cereus, B. subtilis, and C. albicans as fungi. While all compounds show moderate activity against bacteria, no activity against fungi has been investigated. Communicated by Ramaswamy H. Sarma

Experimental and Molecular Docking Studies on the Interaction of a Water-Soluble Pd(II) Complex Containing β-Amino Alcohol with Calf Thymus DNA.

The interaction of water-soluble and fluorescent [Pd (HEAC) Cl2] complex, in which HEAC is 2-((2-((2-hydroxyethyl)amino)ethyl)amino) cyclohexanol, with calf thymus DNA (ct-DNA) has been studied. This study was performed using electronic absorption and fluorescence emission spectroscopies, cyclic voltammetry and circular dichroism analyses, dynamic viscosity measurements, and molecular docking theory. From hypochromic effect observed in ct-DNA absorption spectra, it was found that the Pd(II) complex could form a conjugate with ct-DNA strands through the groove binding mode. The Kb values obtained from fluorescence measurements clearly assert the Pd(II) complex affinity to ct-DNA. The fluorescence quenching of the DNA-Hoechst compound following the successive additions of the Pd(II) complex to the solution revealed that the Pd(II) complex is located in the ct-DNA grooves, and Hoechst molecules have been released into solution; moreover, the resulting measurements from relative viscosity authenticate the Pd(II) complex binding to the grooves. Negative quantities of thermodynamic parameters imply that the Pd(II) complex binds to ct-DNA mainly by the hydrogen bonds and van der Waals forces; also, the Gibbs-free energy changes show the exothermic and spontaneous formation of the Pd(II) complex-DNA system. The electrochemical behavior of the Pd(II) complex in the attendance of ct-DNA was investigated using the cyclic voltammetry method (CV). Several quasi-reversible redox waves were observed along with increasing the anodic/cathodic peak currents, as well as a shift in anodic/cathodic peak potentials. Circular dichroism (CD) observations suggested that the Pd(II)-DNA interaction could alter ct-DNA conformation. The results of molecular modeling confirmed that groove mechanism is followed by the Pd(II) complex to interact with ct-DNA.

A mononuclear PdII complex with Naphcon; crystal structure, experimental and computational studies of the interaction with DNA/BSA and evaluation of anticancer activity

Throughout this study, a new palladium (II) complex, trans-[Pd(Naph)2Cl2], with naphazoline hydrochloride (Naphcon) as an imidazole derivative, 2-(naphthalen-1-ylmethyl)-4,5-dihydro-1H-imidazole;hydrochloride, was synthesized and characterized by elemental analysis, spectroscopic methods (UV–Vis, IR, and 1H NMR) and single crystal X-ray structure analysis. The cytotoxicity of Naphcon and the PdII complex were investigated in vitro against human breast (MCF-7) and cervical epithelial carcinoma (HeLa) cancer cells. The results revealed the higher anticancer activity of complex rather that of Naphcon against MCF-7 cell line. The findings of in vitro studies including fluorescence and UV–Vis spectroscopy, circular dichroism (CD), thermal denaturation and viscosity measurement indicated the interaction of the PdII complex with calf-thymus DNA (CT-DNA) via a combination of covalent and non-covalent interactions, whereas the free Naphcon interacted with CT-DNA mainly through the groove binding mode. Moreover, the ability of Naphcon and the PdII complex to cleave pUC57 plasmid DNA was investigated. In addition, the interaction of both Naphcon and its PdII complex was explored with bovine serum albumin (BSA) by means of absorption and fluorescence spectroscopy. The binding constant (Kb) could be calculated for compounds through these spectroscopic methods. Based on the competitive binding studies using Eosin, Ibuprofen and Digoxin as site markers, the binding site of the PdII complex and Naphcon was found to be located on site-III and I of BSA, respectively. Furthermore, protease activity of compounds was examined under physiological conditions. Finally, to validate all data obtained from biophysical studies, the molecular docking simulation was employed as a computational method.

Synthesis, comparative in vitro antibacterial, antioxidant and UV fluorescence studies of bis indole Schiff bases and molecular docking with ct-DNA and SARS-CoV-2 Mpro.

In this study, synthesis of 15 novel bis indole-based Schiff bases (SBs) 4a-4o was conducted by condensation of 2-(1-aminobenzyl)benzimidazole with symmetrical bis-isatins linked via five alkyl chains (n = 2-6). These were subjected to ADME (absorption, distribution, metabolism and excretion), physiochemical properties, molecular docking, in vitro antibacterial and antioxidant studies. The in silico studies indicated lower toxicity with metabolic stability for nearly all the derivatives proving reliability as drug candidates. The comparative antibacterial study against Staphylococcus aureus and Escherichia coli, also showed a superior inhibition than reference drug and their mono counterparts. The increase in linker alkyl chain length and variation of substituents in indole, further predicted increased inhibition, with maximum value for compound 4o at 50 μg/ml. The in vitro calf thymus DNA (ct-DNA) binding ability of compounds 4c, 4f, 4i, 4l, 4m, 4n, and 4o was evaluated via ultraviolet-visible and fluorescence spectroscopy techniques. A hyperchromic effect was observed with no apparent wavelength shift which predicted for the groove binding mode. A moderate binding constant for 4o, in fluorescence results, confirms groove binding. The molecular docking of 4o with ct-DNA (PDBID:1BNA) and SARS-CoV-2 Mpro (3CL protease, PDBID:6LU7) prove its efficacy as potential DNA binder and antiviral agent.

DNA binding ability and cytotoxicity, cell cycle arrest and apoptosis inducing properties of a benzochromene derivative against K562 human leukemia cells

Chromene and its derivatives are generally spread in nature. Heterocylic-based compounds like chromenes have displayed pharmacological activities. Chromene derivatives are critical due to some biological features such as anticancer activity. CML, chronic myelogenous leukemia, is a fatal malignancy determined by resistance to apoptosis and contains the Philadelphia chromosome. Induction of apoptosis is one of the main approaches in cancer therapy. In this research, benzochromene derivative, 2-amino-4-(4-methoxy phenyl)-4H-benzochromene-3-carbonitrile (4-MC) was tested for cytotoxic and apoptotic induction activities in the human leukemic K562 cell line. The MTT growth inhibition assay was used to determine the cellular growth and survival. Moreover, the binding attribute of 4-MC with double helix DNA was assessed by some spectroscopic and viscosity measurement, and also for docking analysis. 4-MC exhibited good cytotoxicity on K562 cell line and the IC50 value was calculated to be 30 µM. Furthermore, the mechanisms of apoptosis induction were determined morphologically by fluorescence dual staining with acridine orange and ethidium bromide and cell cycle analysis was based on DNA content, as well as the presence of phosphatidyl serine on the outside of the cells by the flow cytometric method. The results showed that 4-MC had potent cytotoxic activity via sub-G1 cell cycle arrest and induction of apoptosis. The experimental and simulation studies reported that 4-MC binds to ctDNA through groove binding mode with the binding constant (K b) of 2.5 × 103 M−1. These data represent a considerable anticancer potential of 4-MC and could be suggested for further pharmacological studies.

Molecular recognition of synthesized halogenated chalcone by calf thymus DNA through multispectroscopic studies and analysis the anti-cancer, anti-bacterial activity of the compounds

The present study aims to elucidate the anti-cancer, antimicrobial activity of synthesized halogenated chalcones (1f, 1h, 1i) and their molecular interaction with calf thymus DNA. All the three compounds were characterized using different spectroscopic tools like FTIR, NMR. DFT and TDDFT computation were performed to support the structural and electronic parameter of the compounds. UV–vis absorbance, steady-state fluorescence, time-resolved fluorescence, circular dichroism, helix melting, molecular docking study reveals that the compounds (1f, 1h, 1i) actively interact with ctDNA via groove binding mode. The binding constants (Kb) were calculated to be 1.29 × 104, 0.54 × 104 and 0.45 × 104 M−1 respectively for compounds 1f, 1h, 1i. The compounds were cytotoxic to almost every cell line (PC3, HeLa, A549, HCT116) tested, having minimal toxicity in normal NKE cell line, among which PC3 cells were more sensitive with an IC50 value of 10 μM. The values were determined using dose response curve and found between 10 and 49 μM for cancer cells and 70 μM for normal cell. Compounds also cause apoptosis in PC3 cells, which was confirmed by Annexin V-FITC/PI assay. Results showed that 1f, 1h, 1i target DNA, to persuade DNA damage mediated cancer cell death. The inhibition zone was formed in the screening test indicating the anti-bacterial activity of 1f, 1h & 1i against model pathogenic bacteria. So the present communication provides quantitative insight of halo-chalcone based anti-cancerous and antimicrobial molecule involving relevant target nucleic acid, which holds future promise in the development of new therapeutic agents.

Exploring the binding mechanism of β-resorcylic acid with calf thymus DNA: Insights from multi-spectroscopic, thermodynamic and bioinformatics approaches

β-resorcylic acid (BR) is a phytochemical which is widely used in the food industry as a flavouring agent and preservative. It has also been found to exhibit antibacterial action against several types of food-borne bacteria. DNA is the main molecular target for many small molecules of therapeutic importance. Hence, the interest is rapidly growing among the researchers to elucidate the interaction between small molecules and DNA. Thus, paving the way to design novel DNA-specific drugs. In this study, an attempt was made to examine the mechanism of binding of BR with calf thymus DNA (ctDNA) with the help of various experiments based on spectroscopy and in silico studies. The spectroscopic studies like UV absorption and fluorescence affirmed the complex formation between BR and ctDNA. The observed binding constant was in the order of 103 M−1 which is indicative of the groove binding mechanism. These findings were further verified by dye-displacement assay, potassium iodide quenching, urea denaturation assay, the study of the effect of ssDNA, circular dichroism and DNA thermal denaturing studies. Different temperature-based fluorescence and isothermal titration calorimetry (ITC) experiments were employed to evaluate thermodynamic parameters. The analysis of thermodynamic parameters supports the enthalpically driven, exothermic and spontaneous nature of the reaction between BR and ctDNA. The forces involved in the binding process were mainly found to be hydrogen bonding, van der Waals and hydrophobic interactions. The results obtained from the molecular docking and molecular dynamics (MD) simulation were consistent with the in vitro experiments, which support the groove binding mode of BR with ctDNA.

The role of both intercalation and groove binding at AT-rich DNA regions in the interaction process of a dinuclear Cu(I) complex probed by spectroscopic and simulation analysis

In this research paper, the synthesis process and characterization of a dinuclear Cu(I) phosphine complex, as well as spectroscopic and simulation analysis of its interaction with DNA helix, are presented. The monoclinic phase [Cu(PPh3)(L0.5)(I)]2 with a tetrahedral molecular geometry was elucidated based on X-ray single-crystal diffraction data. The significant association constant (6.88 × 105) and remarkable hyperchromism as obtained from UV–Visible spectra indicated a high binding affinity of the Cu(I) complex for DNA, which is in accordance with both intercalation and groove binding modes. The results of competitive fluorescence experiments along with molecular docking simulation proved that the planar part of the complex can insert into the core of adenine nucleobases and compete with methylene blue for the intercalative binding sites, while the bulky substituent binds in the minor groove of DNA via replacement of Hoechst molecules at A-T rich regions. According to thermodynamic parameters (the negative values of ΔH° and ΔS°), it is quite clear that the interaction process is enthalpy-favored while disfavored by entropy and van der Walls and hydrophobic forces play a major role in stabilization of right-handed B-DNA form during the interaction, as shown in the circular dichroism spectra. Based on the above findings partial intercalation mode at A-T rich region of DNA was proposed. The cytotoxicity and apoptosis results on MCF-7 cell line indicated positive effect of the Cu(I) complex in controlling growth and viability of breast cancer more than cisplatin.