DNA Interaction Properties Research Articles

Recent advances on the DNA interaction properties of Schiff bases and their metal complexes

Cancer has become the second leading reason for death in the world. Cell biology states that the bulk of anti‐cancer medications focuses on DNA. A study of how complexes of metals interact with DNA is crucial in creation of the effective chemotherapy drugs. The interactions of DNA with Schiff base and their metal complexes are a thrust area for many researchers, and many papers have reported on them. An amino molecule reacts with carbonyl group to form a variety of chemicals called Schiff bases. Many studies have shown that Schiff bases have compounds that affect biological processes. Due to their potential use as novel reagents for biotechnology and medicine, the research of interactions between transition metal complexes and nucleic acids has grown significantly during the past few decades. It was shown that several metal Schiff base complexes may intercalate DNA. Small molecules can attach themselves to DNA through different ways, such as intercalation and groove binding. The main method to measure nuclease activity was gel electrophoresis, and the ligand alone had much lower activity than the complex. To set the stage for this analysis, a brief overview of Schiff bases and their complexes is provided. Further, this review provides an overview of the DNA interactions brought forth by Schiff base metal complexes. It also draws attention to new developments in the study of Schiff bases and their metal complexes and their prospective use as a bioactive core for DNA cleavage and binding.

New type paraben decorated mono- and dispirocyclotriphosphazene compounds: Synthesis, characterization and DNA binding studies

Parabens are a group of chemical preservatives that are widely used in the cosmetics, pharmaceutical, and food industries. Although some studies have raised concerns about potential health risks associated with parabens, it is important to note that the presence of parabens in tumor tissue does not provide conclusive evidence that parabens cause cancer. This is an area that requires further research. For this purpose, six new mono- and dispirocyclotriphosphazene compounds decorated with paraben were synthesized and designed for the first time. Their structures were identified by MALDI-TOF MS, 1H, 31P NMR and FT-IR spectroscopy. Moreover, the molecular structure of Compound 8 was determined by X-Ray crystallography. The DNA interaction properties of the targeted molecules were investigated via agarose gel electrophoresis.

Synthesis, antioxidant, DNA interaction, electrochemical, and spectroscopic properties of chromene-based Schiff bases: Experimental and theoretical approach

Two chromene-based Schiff base ligands were synthesized by the condensation of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde with 2-aminodiphenylamine and 1,8-diaminonaphthalene: (E)-2,2-dimethyl-6-(((2-(phenylamino)phenyl)imino)methyl)-2H-chromen-5-ol (2) and (E)-6-(((8-aminonaphthalen-1-yl)imino)methyl)-2,2-dimethyl-2H-chromen-5-ol (3). The compounds were characterized by Fourier transform infrared (FT-IR), absorption (UV-Vis) and nuclear magnetic resonance (NMR) spectroscopies, in addition to mass spectrometry (MS) analyses; the results of which were rationalized using density functional theoretical (DFT) calculations. Antioxidant activity of the Schiff bases was determined using the DPPH free radical scavenging and CUPric Ion Reducing Antioxidant Capacity (CUPRAC) assays. Compound 3 (IC50 = 14 μM) showed greater free radical scavenging ability than compound 2 (35 μM), and was also more effective than ascorbic acid and Trolox. DFT studies indicate that the HAT mechanism is favored over SET for DPPH scavenging. Both compounds exhibited stronger Cu(II) ion reducing capacity than Trolox and ascorbic acid with Trolox equivalent activity coefficient (TEAC) values of 2.0 and 1.6 for compounds 2 and 3, respectively. Furthermore, DNA cleavage and binding properties were determined using gel electrophoresis, UV-Vis spectroscopy, and cyclic voltammetry. The compounds showed copper-mediated cleavage of plasmid DNA and strong binding to DNA, with binding constants on the order of 104 M−1. The strength of DNA binding was verified by molecular docking analysis using two DNA models: a B-DNA dodecamer (-8.4 to -9.3 kcal/mol) and a hexamer (-7.8 to -7.9 kcal/mol). Overall, the chromene Schiff bases show promise as antioxidant and DNA binding agents.

Effect of Cu(II) compound containing dipicolinic acid on DNA damage: a study of antiproliferative activity and DNA interaction properties by spectroscopic, molecular docking and molecular dynamics approaches

A polymeric compound formulized as [Cu(µ-dipic)2{Na2(µ-H2O)4]n.2nH2O (I), where dipic is 2,6-pyridine dicarboxylic acid (dipicolinic acid, H2dipic), was synthesized by sonochemical irradiation. The initial in-vitro cytotoxic activity of this complex compared with renowned anticancer drugs like cisplatin, versus HCT116 colon cell lines, shows promising results. This study investigated the interaction mode between compound (I) and calf-thymus DNA utilizing a range of analytical techniques including spectrophotometry, fluorimetry, partition coefficient analysis, viscometry, gel electrophoresis and molecular docking technique. The results obtained from experimental methods reveal complex (I) could bind to CT-DNA via hydrogen bonding and van der Waals forces and the theoretical methods support it. Also, complex (I) indicates nuclease activity in the attendance of H2O2 and can act as an artificial nuclease to cleave DNA with high efficiency. Communicated by Ramaswamy H. Sarma

DNA interaction, cytotoxic and phototoxic properties of new water‐soluble zinc (II) phthalocyanines

In this paper, we have synthesized water‐soluble peripherally tetra and octa‐({6‐[3‐(dimethylamino)phenoxy]hexyl}oxy) groups substituted zinc (II) phthalocyanines (DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ). Also, we have investigated ct‐DNA binding, supercoiled plasmid DNA cleavage properties of DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ by using spectrophotometric and electrophoretic methods. On the other hand, cytotoxic and phototoxic effects of DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ were examined using (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay on human lung adenocarcinoma (A549) cell lines. In UV–Vis absorption studies, hypochromism was observed about 18% for DM‐C6‐ZnQ and 57% for o‐DM‐C6‐ZnQ on addition of increasing concentrations of ct‐DNA. The intrinsic binding constant (Kb) values of DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ were 3.82 (±0.14) × 104 M−1 and 2.34 (±0.05) × 105 M−1, respectively. The supercoiled plasmid DNA cleavage studies showed that DM‐C6‐ZnQ and o‐DM‐C6‐ZnQ had no DNA damage actions in the dark. On the other hand, they caused DNA damage depending on the light dose. In the MTT assay, the compounds had low cytotoxic properties on A549 cell lines, but they showed significant phototoxic actions. These results reveal that the compounds interact with DNA and have phototoxic properties; it has been determined that they have the potential to be photosensitizing agents for photodynamic therapy.

Synthesis of water‐soluble BODIPY dyes and investigation of their DNA interaction properties and cytotoxicity/phototoxicity

AbstractIn this study, water‐soluble BODIPY dyes (BDPY‐4,BDPY‐5) bearing dimethylamino and diethylamino groups were synthesized for the first time. The DNA interaction and nuclease effect of two water‐soluble BODIPY dyes were examined using absorption, competitive binding experiments, and agarose gel electrophoresis. Then, cytotoxicity and phototoxicity of the compounds were determined against A549 cells by MTT cell viability assay. The ultraviolet–visible (UV–vis) spectra ofBDPY‐4andBDPY‐5displayed hypochromism and absorption maxima shifted to the red region. In addition,Kbvalues of the compounds were calculated as 2.23 × 104and 4.84 × 104 M−1, respectively. An high‐performance liquid chromatography (HPLC) instrument without a column was used to conduct competitive binding experiments for the first time. The approach prevented the decrease in the response due to dilution and enabled the analysis to be carried out in a short time. Upon increasing concentrations of the compounds, the emission intensity of EB‐DNA significantly decreased. These obtained results suggested that the compounds bound to CT‐DNA with intercalative mode. At the same time, the Stern–Volmer constants were determined as 1.80 × 106and 1.79 × 106 M−1forBDPY‐4andBDPY‐5, respectively, which is coherent with intercalative binding mode. The compounds did not display noticeable photonuclease actions with light irradiation.BDPY‐4andBDPY‐5showed moderate phototoxic properties on light irradiation.

Novel β-lactam antibiotic derivative and its complexes: DFT, frontier energy levels, DNA interaction, docking, physicochemical and antimicrobial properties

Ampicillinacetylacetone Schiff base (HAA) and its complexes with Co(II), Ni(II), Cu(II), Eu(III) and Gd(III) obtained in pure form. The obtained compounds characterized by CHNM%, FTIR, UV–Vis, Fluorescence, 1HNMR, Mass spectra, DTA, TGA, Magnetic susceptibility, X-ray, AAS, melting point, solubility in different solvents and the conductivity of 0.001 M in DMSO. The obtained data indicate the formation of the target complexes in the form [Co(AA)(H2O)2]NO3.2H2O, [Ni(AA)(H2O)2]Cl.4H2O, [Cu(AA)]Cl.2.5H2O, [Eu(AA)(H2O)Cl]Cl.6H2O and [Gd(AA)(H2O)(NO3)]NO3.2H2O. Co and Ni gave Oh structure while Cu gave square planar form. The Crystal field parameters calculated and discussed for the target complexes. Molecular modelling, molecular mechanics and DFT calculation carried out to the synthesized compounds. The x-ray analysis indicates the nanoparticle behaviour for the Cu-AA complex with an orthorhombic structure. The interactions of the synthesized complexes with DNA moiety investigated with means of spectrometric titration (UV–vis. spectra) and by using fluorescence spectroscopy. Antimicrobial activities of the synthesized compounds screened using the disc diffusion method. HAA and Cu-AA gave activity exceeded the Ampicillin. The docking work carried using the targeting protein of Escherichia coli FabH (PDB code: 1HNJ). The obtained binding energy compared and discussed in terms of the in vitro studies.

Electrophoresis and Biosensor-Based DNA Interaction Analysis of the First Paraben Derivatives of Spermine-Bridged Cyclotriphosphazenes

Cancer is the uncontrolled growth of abnormal cells via malignant cell division and rapid DNA replication. While DNA damaging molecules can cause cancer, their role as anticancer drugs are very significant. For this purpose, the novel series of paraben substituted spermine bridged(dispirobino) cyclotriphosphazene compounds 2-6 were synthesized for the first time, and their structures were characterized by various spectroscopic techniques. The solid-state structures and geometries of compounds 2-6 were determined using single-crystal X-ray structural analysis. In addition, it was confirmed by TGA that all compounds 1-6 showed high thermal stability. Two methods were used in order to investigate DNA interaction properties of the targeted molecules. While biosensor-based screening test that measures DNA hybridization efficiency on a biochip surface, the agarose gel electrophoresis method examines the effect of compounds on plasmid DNA structure. The results collected from the automated biosensor device and agarose gel electrophoresis have indicated that compounds 1, 5, and 6 showed higher DNA damage than the compounds 2-4. According to the biosensor results, compounds 1, 5, and 6 showed 85%, 69%, and 77% activity, respectively.

DNA interaction and anticancer properties of new peripheral phthalocyanines carrying tosylated 4-morpholinoaniline units

In this paper, tosylated 4-morpholinoaniline units fused peripherally tetra-substituted free-base (5), copper(II) (6), zinc(II) (7), cobalt(II) (8) and magnesium(II) (9) phthalocyanines (Scheme 1) were reported and these new phthalocyanine conjugates were characterized through Fourier Transform–Infrared (FT–IR) with ATR sampling accessory, Mass Spectra Analysis [Matrix Assisted Laser Desorption/Ionization–Time of Flight–Mass Spectral (MALDI–TOF–MS)] and Ultraviolet–visible (UV–vis) (for all new phthalocyanines), elemental analysis, as well as 1H and 13C NMR spectroscopic techniques [for the compounds (2), (4), (5), (7) and (9)]. The potential utilization of the new peripheral phthalocyanine compounds (7–9) as the new pharmaceutical agents in PDT applications (in oncology and molecular biology) were determined in aspects of pBR322 plasmid DNA cleavage on agarose gel electrophoresis. The results showed that compound (7) cleaved pBR322 plasmid DNA with irradiation. Compound (7) displayed hypochromism without any shift on the addition of increasing concentrations of ct-DNA and Kb of compound (7) was calculated as 2.45 ± (0.20) × 104 M−1. In photochemical studies, the ΦΔ value of compound (7) was determined as 0.11. The cytotoxic/phototoxic properties of compound (7) which had the best photocleavage effects among tested compounds were investigated using MTT assay toward human colorectal (HCT-116) and cervical (HeLa) cancer cells. The cell viabilities of compound (7) were found to be 73 ± 1.6% (HCT-116) and 65 ± 5.5% (HeLa) at 100 µM with irradiation.

Novel water soluble BODIPY compounds: Synthesis, photochemical, DNA interaction, topoisomerases inhibition and photodynamic activity properties

In this study, BODIPY compounds (2, 3, 5 and 6) bearing 3,4-bis(3-pyridin-3-ylpropoxy)benzyl, 4-(3-pyridin-3-ylpropoxy)benzyl groups were synthesized for the first time and further functionalized in a Knoevenagel condensation reaction with 3,4-bis(3-pyridin-3-ylpropoxy)benzaldehyde and 4-(3-pyridin-3-ylpropoxy)benzaldehyde. The water soluble derivatives of BODIPY compounds (3a and 6a) were synthesized by treating BODIPY compounds 3 and 6 with excess iodomethane in DMF. The photochemical properties and DNA binding modes of 3a and 6a were determined using ct-DNA by UV–Vis spectrophotometer and viscometer. DNA cleavage and topoisomerases inhibition properties were studied DNA using agarose gel electrophoresis. Their topoisomerase inhibition mechanisms were investigated at molecular level and correlations with the in vitro results were searched for using molecular docking method. In addition, cytotoxicity and phototoxicity of both compounds were performed on colorectal cancer cells (HCT-116) using MTT assay for 24 h. Annexin V-FITC/PI test was performed to determine the cell death mechanism of 6a induced by irradiation. Finally, 6a-loaded liposomes (LP6a) and PLGA nanoparticles (NP6a) were prepared and their cytotoxic and phototoxic effects were evaluated by MTT assay. The results claimed that 6a had great potential as photosensitizer agent for colorectal cancer owing to its photochemical, DNA interaction and phototoxic properties.

Theoretical study on the DNA interaction properties of copper(II) complexes

Theoretical studies on DNA-cleavage and DNA-binding properties of a series of Cu(II) complexes [Cu(bimda)(diimine)] 1–5 have been carried out by density functional theory (DFT). The optimized structures of Cu(II) complexes were docked into parallel, antiparallel and mixed G-quadruplexes, with which the binding energies of complexes 1–5 were obtained. The cytotoxicities of these complexes can be predicted preliminarily by the binding energies. To explore the energy changes of Cu(II) complexes in duplex DNA, the optimized structures of these complexes were docked into the duplex DNA, and the obtained docking models were further optimized using QM/MM method. The DNA-cleavage abilities of complexes 1–5 can be predicted accurately and explained reasonably by the computed intra-molecular reorganization energies of these complexes. This work reported here has implications for the understanding of the interaction Cu(II) complexes with the DNA, which might be helpful for the future directing the design of novel anticancer Cu(II) complexes.

Palladium(II) and ruthenium(II) complexes of benzotriazole functionalized N-heterocyclic carbenes: Cytotoxicity, antimicrobial, and DNA interaction studies

In the present study, four palladium and four ruthenium complexes were synthesized with benzotriazole substituted N-heterocyclic carbene ligands. The structures of complexes were established by appropriate spectroscopic methods and elemental analyses. In addition, the crystal structure of a PdNHC complex (1c) was reported. Anticancer, antimicrobial and DNA interaction properties of the complexes were examined. Antimicrobial effects of the complexes were tested against two bacteria strains and one fungi strain. Cytotoxic effects of the complexes were tested against human breast (MCF-7) and colorectal (Caco-2) cancer cell lines and non-cancer mouse fibroblast (L-929) cell lines. Ruthenium complexes were found as more cytotoxic than palladium complexes against cancer cell lines. Especially, benzyl containing, benzimidazole-based ruthenium complexes (3c and 3d) were found as non-cytotoxic against non-cancer L-929 cell lines while performing comparable cytotoxicity against Caco-2 cancer cell lines with cisplatin. In addition, DNA interaction studies were performed with pBR322 plasmid DNA and ctDNA and results showed that both palladium and ruthenium complexes have weaker ability to interact with DNA than cisplatin. The results from this study showed that although the cytotoxic properties of the complexes are not stronger than cisplatin, selectivity of benzyl containing benzimidazole-based ruthenium-NHC complexes against Caco-2 cell lines provides them an advantage, and they deserve further research in the treatment of human colorectal cancer.

Synthesis of water soluble silicon phthacyanine, naphthalocyanine bearing pyridine groups and investigation of their DNA interaction, topoisomerase inhibition, cytotoxic effects and cell cycle arrest properties

In this work, axially [3,5-bis(3-pyridin-4-ylpropoxy)phenyl]methoxy groups substituted silicon (IV) phthalocyanine 2, napthalocyanine 3 and their water soluble derivatives 2a, 3a were synthesized and DNA interaction, topoisomerases inhibitory properties, cytotoxicity against five carcinoma cell lines of water soluble derivatives were examined. The calf thymus DNA (CT-DNA) binding properties of 2a and 3a were monitored using UV–Vis spectroscopy and agarose gel electrophoresis. The results showed that the compounds interacted to CT-DNA via intercalation with Kb values of 3.94 ± (0.15) × 106 and 1.08 ± (0.10) × 105 M−1. In DNA cleavage studies, the compounds cleaved to supercoiled pBR322 plasmid DNA significantly with irradiation as compared to without irradiation. The results of topoisomerases studies claimed that both compounds had inhibitory effects against topoisomerases. In the cytotoxicity studies, the CC50 values of the compounds were found in range of 2.15–52.97 μM against to five carcinoma cell lines. The SI values of 3a were found as 4.51, 1.43 and 3.66 against A549, BT20 and SK-MEL 128 cell lines. The cell cycle arrest was investigated against A549 cells by flow cytometry and obtained results indicated that both compounds induce cell cycle arrest at G0/G1 phase. All of obtained results demonstrated that 3a had lead anticancer agent toward lung, breast and melanoma due to its high selectivity to cancer cell lines.

DNA interaction of ruthenium(ii) complexes with imidazo[4,5-f][1,10]phenanthroline derivatives.

In this paper, the DNA interaction properties of four Ru(ii) polypyridyl complexes, [Ru(bpy)2(pip)]2+ (1), bpy = 2,2'-bipyridine, pip = 2-phenyl-imidazo[4,5-f][1,10]phenanthroline, [Ru(bpy)2(nip)]2+ (2), nip = 2-naphthyl-imidazo[4,5-f][1,10]phenanthroline, [Ru(bpy)2(aip)]2+ (3), aip = 2-(9-anthryl)-imidazo[4,5-f][1,10]phenanthroline and [Ru(bpy)2(pyip)]2+ (4), pyip = 2-(1-pyrenyl)-imidazo[4,5-f][1,10]phenanthroline, were investigated by spectral titration. The intensity increases in the MLCT band of the complexes and the decrease in absorption due to the DNA secondary structure was attributed to DNA condensation by these complexes. The DNA condensing behavior of these complexes was investigated in more detail by gel electrophoresis (GAR), dynamic light scattering (DLS), zeta potential, atomic force microscopy (AFM), and transmission electron microscopy (TEM). The results suggest that the concentration of the complex plays a critical role in its DNA intercalating and DNA condensing behavior. Meanwhile, the aryl units in the ligands of complex 1-4 also have a large effect on their interactions with DNA.

Design, synthesis and biological evaluation of novel benzo- and tetrahydrobenzo-[h]quinoline derivatives as potential DNA-intercalating antitumor agents

A new series of benzo- and tetrahydro benzo-[h]quinoline bearing a flexible (dimethylamino)ethylcarboxamide side chain was designed and synthesized as DNA-intercalating antitumor agents. The cytotoxic activity of the synthesized compounds was evaluated against four human cancer cell lines including MCF-7, A2780, C26 and A549. In general, saturated quinolines (tetrahydrobenzo[h]quinolines) exhibited more cytotoxicity compared to their corresponding unsaturated quinolines (benzo[h]quinolines). Compound 6e showed significant cytotoxicity against all four human cancer cell lines with IC50 values ranging from 1.86 to 3.91 μM. The interaction of the selected compounds showed significant cytotoxicity (6b, 6e, 6i and 6j) with calf thymus DNA (CT-DNA) was studied by UV and florescent spectroscopy. In general, benzo[h]quinolines showed higher interacting effect with DNA than their corresponding saturated tetrahydrobenzo[h]quinolines. Compound 6i exhibited the most DNA intercalating effects among the series. The apoptotic induction potential of the most cytotoxic compounds (6e, 6b and 6i) in A549 cells was studied using Annexin V-FITC/Propidium iodide staining assay. Compound 6e which showed the most cytotoxic effect against A549 cancer cells also exhibited stronger apoptotic induction activity in comparison with 6b and 6i.The docking was performed in order to study the DNA interaction properties of these compounds. According to the computational data, these compounds can interact with DNA as DNA-intercalating agents.

Chromomycin A2 potently inhibits glucose-stimulated insulin secretion from pancreatic β cells.

Modulators of insulin secretion could be used to treat diabetes and as tools to investigate β cell regulatory pathways in order to increase our understanding of pancreatic islet function. Toward this goal, we previously used an insulin-linked luciferase that is cosecreted with insulin in MIN6 β cells to perform a high-throughput screen of natural products for chronic effects on glucose-stimulated insulin secretion. In this study, using multiple phenotypic analyses, we found that one of the top natural product hits, chromomycin A2 (CMA2), potently inhibited insulin secretion by at least three potential mechanisms: disruption of Wnt signaling, interference of β cell gene expression, and partial suppression of Ca2+ influx. Chronic treatment with CMA2 largely ablated glucose-stimulated insulin secretion even after washout, but it did not inhibit glucose-stimulated generation of ATP or Ca2+ influx. However, by using the KATP channel opener diazoxide, we uncovered defects in depolarization-induced Ca2+ influx that may contribute to the suppressed secretory response. Glucose-responsive ERK1/2 and S6 phosphorylation were also disrupted by chronic CMA2 treatment. By querying the FUSION bioinformatic database, we revealed that the phenotypic effects of CMA2 cluster with a number of Wnt-GSK3 pathway-related genes. Furthermore, CMA2 consistently decreased GSK3β phosphorylation and suppressed activation of a β-catenin activity reporter. CMA2 and a related compound, mithramycin, are known to have DNA interaction properties, possibly abrogating transcription factor binding to critical β cell gene promoters. We observed that CMA2 but not mithramycin suppressed expression of PDX1 and UCN3. However, neither expression of INSI/II nor insulin content was affected by chronic CMA2. The mechanisms of CMA2-induced insulin secretion defects may involve components both proximal and distal to Ca2+ influx. Therefore, CMA2 is an example of a chemical that can simultaneously disrupt β cell function through both noncytotoxic and cytotoxic mechanisms. Future therapeutic applications of CMA2 and similar aureolic acid analogues should consider their potential effects on pancreatic islet function.

Synthesis, characterization and DNA interaction properties of the novel peripherally tetra 4-(3-methyl-4-(3-morpholinopropyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl) substituted water soluble Zn(II) and Cu(II) phthalocyanines

The triazol compound 3-methyl-4-(3-morpholinopropyl)-1H-1,2,4-triazol-5(4H)-one (3), phthalonitrile compound 4-(3-methyl-4-(3-morpholinopropyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)phthalonitrile (5), peripherally tetra substituted zinc(II) (6) and copper(II) (7) phthalocyanines and their water soluble quaternized derivatives (6a) and (7a) were synthesized for the first time in this study. These novel compounds were characterized with FT-IR, 1H NMR, 13C NMR, UV–Vis and mass spectroscopy. The absorption titration, and thermal denaturation studies were preferred to investigate the interaction mode of the water soluble quaternized tetra substituted peripherally phthalocyanines zinc(II) (6a) and copper (II) (7a) with CT-DNA. 6a and 7a bound to CT-DNA with Kb values of 6.53 ± (0.04) × 104 M−1 and 1.14 ± (0.02) × 104 M−1, respectively. The observed ΔTm of CT-DNA with the compounds were elucidated as 7.55 °C and 5.75 °C. In addition, supercoiled pBR322 plasmid DNA was used to determine cleavage properties of the compounds by agarose gel electrophoresis. The compounds had no cleavage activities in the absence of oxidizing agents in the dark whereas; the both compounds had excellent photo cleavage activities in the absence and presence of oxidizing agents such as H2O2, ME and AA. The results of electrophoresis indicated that singlet oxygen is responsible for the cleavage activities of the water soluble quaternized tetra substituted peripherally phthalocyanines zinc(II) (6a) and copper (II) (7a) with irradiation. These results showed that both compounds may be potential anticancer drug for photodynamic therapy.

Allosterism and signal transfer in DNA.

We analysed the basic mechanisms of signal transmission in DNA and the origins of the allostery exhibited by systems such as the ternary complex BAMHI–DNA–GRDBD. We found that perturbation information generated by a primary protein binding event travels as a wave to distant regions of DNA following a hopping mechanism. However, such a structural perturbation is transient and does not lead to permanent changes in the DNA geometry and interaction properties at the secondary binding site. The BAMHI–DNA–GRDBD allosteric mechanism does not occur through any traditional models: direct (protein-protein), indirect (reorganization of the secondary site) readout or solvent-release. On the contrary, it is generated by a subtle and less common entropy-mediated mechanism, which might have an important role to explain other DNA-mediated cooperative effects.

DNA interaction analysis of fluorenylidene double bridged cyclotriphosphazene derivatives

Abstract DNA is a target molecule for anticancer drug development, and investigation on DNA interactions with synthesized potential drugs has great importance in order to discover new drug candidates, hence in this study an electrochemical biosensor has been used to perform quantitative analysis of DNA/compound interactions. In this study, full paraben substituted fluorenylidene double bridged cyclotriphosphazene compounds (9–13) were synthesized for the first time and their effect on DNA were investigated using an automated biosensor device MiSens®. The reaction of fluorenylidene double bridged cyclotriphospazene (FDBC) compound (3) with parabens: methyl 4-hydroxybenzoate, (4); ethyl 4-hydroxybenzoate, (5); propyl 4-hydroxybenzoate, (6); butyl 4-hydroxybenzoate (7), benzyl paraben (8) were performed, respectively. Compounds 9–13 were obtained and fully characterizated by mass spectrometry, 31P NMR and 1H spectroscopy. Biosensor based screening tests were used to investigate DNA interaction properties of the newly synthesised compounds by measuring DNA hybridization efficiency on the biochip surface. The effect of the compounds to the plasmid DNA structure were analyzed by agarose gel electrophoresis, in addition the antimicrobial activities of the compounds have been investigated. The biosensor assay and the agarose gel electrophoresis investigation indicated DNA/compound interaction for the compounds 12 and 13 none of the compounds has shown antimicrobial activity.

Redox, spectroscopic, photo-induced ligand exchange, and DNA interaction studies of a new Ru(II)Pt(II) bimetallic complex

A new bimetallic complex, [Ru(biq)2(dpp)PtCl2](PF6)2 (where biq = 2,2′-biquinoline and dpp = 2,3-bis(2-pyridyl)pyrazine), containing a cis-PtCl2 moiety coupled to a sterically strained Ru(II)-based chromophore was designed, synthesized, and investigated with respect to its spectroscopic, redox, photo-induced ligand exchange, and DNA-interaction properties. The electrochemistry of the designed complex was found to be consistent with the bridging coordination of the dpp ligand and formation of the bimetallic complex. The complex displays intense ligand-based π → π* transitions in the UV region and metal-to-ligand charge-transfer transitions (MLCT) in the visible region. The loss of bridging coordination of the dpp ligand and formation of complexes, [Ru(biq)2(CH3CN)2]2+ and [Pt(dpp)(CH3CN)2]2+ was observed when an acetonitrile solution of the metal complex was irradiated with visible light (λirr ≥ 550 nm). The designed complex displays covalent binding with DNA in dark through the cis-PtCl2 moiety, as confirmed by agarose gel electrophoresis. Upon photoirradiation, the complex dissociates into two DNA-binding moieties and displays covalent binding through: (i) a cis-PtL2 subunit of [Ptdpp(L)2]2+ and (ii) open coordination sites of the ruthenium of [Ru(biq)2(L)2]2+ (L = solvent). The designed complex represents the first Ru(II)Pt(II) complex that undergoes photo-induced ligand exchange and displays multifunctional interactions with DNA upon photoirradiation.