Intercalative Binding Mode Research Articles

Characterization studies of novel series of cobalt (II), nickel (II) and copper (II) complexes: DNA binding and antibacterial activity

In the present investigation metal (II) complexes containing binuclear Co (II), mono nuclear Ni (II), and Cu (II) with ligand 2E-N-phenyl-2-[([1,3]thiazolo[3,2-a]benzimidazol-2yl) methylidene]hydrazine-1-carbothioamide moiety were synthesized in ethanolic medium, recrystallized and investigated for their biological properties. The carbothioamide was derived from the reaction of benzo [4, 5] imidazo [2, 1-b] thiazole-2-carbaldehyde and 4-phenyl-3-thiosemicarbazide at reflux temperature. The newly formed compounds were characterized by 1H-nuclear magnetic resonance (1H-NMR), 13C-nuclear magnetic resonance (13C-NMR), Fourier transformed infrared spectroscopy (FT-IR), ESR spectroscopic techniques and elemental analysis. Ligand containing “O” and “S” donor atoms participated in coordination with metal (II) complexes and are confirmed by FT-IR, electronic absorption spectra, 1H-NMR data. DNA binding properties of these metal complexes were investigated by ESR, magnetic moments and electronic absorption spectroscopy. Antibacterial studies, DNA binding constants of the complexes indicated intercalative binding mode involving strong aromatic chromophoric groups and base pairs of DNA. All the complexes (2a, 2b and 2c) showed intercalative binding with DNA and DNA cleavage was studied in presence and absence of H2O2 which was observed for copper (II) complex. Antibacterial study results showed that cobalt complex inhibit the growth of Staphylococcus epidermis, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli with MIC values of 7.98 µg/mL, 8.12 µg/mL, 7.34 µg/mL, and 7.56 µg/mL respectively. Metal (II) complexes exhibit higher antibacterial activity than the parent ligand.

The novel zinc(II) complex with dibromo substituted Schiff base and its biological activity

Schiff base 3,5-dibromo-N-(8-quinolyl)salicylaldimine (HqsalBr2) and its zinc(II) complex, [Zn(qsalBr2)2], have been synthesized and characterized using spectroscopic techniques and single crystal X-Ray crystallography. The interaction of the complex with calf thymus DNA (CT-DNA) was investigated by electronic absorption and luminescence titration methods. The results reveal the intercalative mode of binding between the synthesized complex and CT-DNA with binding constant (Kb) of 2.00 × 106 M−1. The complex also exhibits capability in the competitive reaction with the standard ethidium bromide (EB) and provides favourable quenching constant value (Kq) of 7.91 × 1011 M−1s−1. Anti-lung cancer activity against A549 cell line was examined and zinc(II) complex performed the ability in the inhibition of this cancer cell growing.

Peculiar DNA partial threading intercalative ability of tetradentate copper complex based on ONO hydrazone backbone and an ancillary ligand

Multidentate copper metal complexes have been in the limelight in the area of DNA interaction studies exhibiting intercalation, groove binding and cross linking modes. Design of metal complex based on the versatile ligands decides their mode of DNA binding behavior. Based on this, a tetradentate Copper (II) complex, [Cu(L)(4,4’-bpy)], is synthesized using ONO hydrazone ligand and ancillary ligand, 4,4’-bipyridine. It is characterized by physico-chemical and UV-Visible, FTIR, Mass and EPR spectroscopic techniques. The binding pattern of the characterized complex with DNA has been assessed by UV absorption and fluorescence spectral titrations as well as viscosity studies and it has exhibited peculiar threading intercalation. The binding constant, Kb value of the synthesized complex was found to be (4.38 ± 0.09) × 104 M− 1, greater than that of the hydrazone ligand (Kb = 2.29 × 104 M−1) and lesser than the classical intercalator ethidium bromide - EtBr (Kb = 107). The fluorescence quenching assays in the presence of ethidium bromide and viscometric studies show threading intercalative mode of binding of the complex to the DNA base pairs. Molecular docking studies further supports such a binding pattern with the bipyridine ring of the complex intercalating with deoxycytosine nucleobase of DNA. ADME (Absorption, Distribution, Metabolism and Excretion) parameters of the complex and ligand were predicted to get an idea of drug likeliness and to correlate the structural properties with semi DNA intercalative pattern of the same.

New Mg(II) and Ca(II) Mixed Strontium Squarates: Structural Characterization, DNA/BSA Interaction, Antioxidant and Anticancer Activities

New mixed alkaline earth metal squarates, viz [Sr0.965Mg0.035(C4O4)(H2O)2]·H2O—(1) and [Sr0.88Ca0.12(C4O4)(H2O)3]—(2) have been synthesized and characterized by single-crystal X-ray diffraction, thermal analysis, and biological studies, EB-CTDNA binding, BSA binding, antioxidant and cytotoxicity activity. The complexes 1 and 2 crystallized in triclinic and monoclinic space groups with eight and nine coordination number, respectively, from the reaction mixture of squaric acid and the respective metal nitrates in aqueous medium at pH 7. The complexes on thermal analysis show that they yield mixed metal carbonates at 544 °C as residue. Their interaction with EB-CTDNA evaluated by emission method substantiates the intercalative mode of binding. The protein binding (BSA) study by the fluorescence quenching method reveals that the complexes bind strongly with BSA. Antioxidant property analysis shows that they exhibit a strong radical scavenging ability against ABTS, DPPH and NO radicals. The in vitro cytotoxicity of the complexes examined for human breast cancer (MCF-7) and lung cancer (A549) cell lines exhibit substantial cytotoxic property. AO/EB and DAPI staining methods support that they induce apoptosis and nuclear fragmentations in MCF-7 and A549 cell lines.

Copper(II) complexes with meclofenamate ligands: Structure, interaction with DNA and albumins, antioxidant and anticholinergic activity

The interaction of copper(II) with the non-steroidal anti-inflammatory drug sodium meclofenamate (Na-mclf) in the presence or absence of the nitrogen-donor co-ligands pyridine (py) or 2,2′-bipyridylamine (bipyam), yielded the novel Cu(II) complexes [Cu2(mclf-O,O′)4(MeOH)2]·2MeOH (1·2MeOH), [Cu(mclf-O)2(py)3]·H2O·0.5MeOH (2·H2O·0.5MeOH) and [Cu(mclf-O,O′)2(bipyam)] (3). The characterization of the complexes was achieved by various techniques, including single-crystal X-ray crystallography. In order to study the binding mode and strength of the complexes to calf-thymus (CT) DNA, various techniques were employed which suggested intercalation between the DNA-bases as the most possible interaction mode. Competitive studies with ethidium bromide (EB) revealed the ability of the complexes to displace the EB from the EB-DNA adduct, verifying the intercalative binding mode. The affinity of the complexes to bovine and human serum albumin proteins (SAs) was investigated by fluorescence emission spectroscopy and the corresponding binding constants bear relatively high values, showing that the complexes bind tightly and possibly reversibly to SAs. The antioxidant activity of the complexes against 1,1-diphenyl-picrylhydrazyl (DPPH), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals and the ability to reduce H2O2 proved to be of significant magnitude. The in vitro inhibitory activity against the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was evaluated, in order to assess the anticholinergic ability of the complexes, which appeared promising.

First electroanalytical studies of methoxyfenozide and its interactions with dsDNA

The widespread use of pesticides is one of the major health and environmental concerns. There is an urgent need to develop improved analytical methodologies as well as for a deep insight into the mechanism behind the interaction between pesticides and the nucleic acids of living organisms. In the present work, the electrochemical behavior of the diacylhydrazine insecticide methoxyfenozide ( Met ) on a boron-doped diamond electrode and its interaction with double-stranded DNA (dsDNA) were investigated for the first time by applying cyclic voltammetry and square-wave (SW) voltammetry. The influence of numerous factors, such as composition of the supporting electrolyte, its pH, and voltammetric parameters, was analyzed. Under the optimized conditions, a simple and sensitive SW voltammetric procedure was developed for the determination of Met . Quantification was found to be linear from 5.0 × 10 −7 to 7.0 × 10 −5 mol L −1 , with a detection limit of 1.4 × 10 −7 mol L −1 . The application of the developed voltammetric methodology for the analysis of tap water, river water and grape juice was tested with spiked samples. Studies on the interaction between methoxyfenozide and double-stranded salmon sperm DNA were conducted using both voltammetric and spectroscopic techniques. The results obtained indicated the dominance of the intercalative binding mode between Met and dsDNA. The binding constants of the formed complex were calculated based on the changes in the electrochemical and spectroscopic behaviors of Met in the presence of dsDNA. • First electroanalytical study of insecticide methoxyfenozide. • Successful application of proposed methodology in spiked samples analysis • Cheap, fast, and environmentally friendly methodology. • Electrochemical and spectroscopic assay of the interaction between Met and dsDNA. • The dominance of the intercalative binding mode between Met and dsDNA.

Trizbenzim, Cu-Trizbenzim and Zn-Trizbenzim as G-Quadruplex Inducing and Stabilizing Compounds on Human Telomeric Sequence and their Anticancer Properties.

The benzimidazole and their derivatives have rich biological relevance with respect to available natural amino acids and their role in protein folding and quaternary conformations. Thus the ligand trizbenzim and their Cu(II) and Zn(II) metal complexes were prepared to induce G-quadruplex conformation even under no-salt conditions with remarkable anticancer activities. The ligand N,N',N''-Tris-(1H-benzoimidazol-2-ylmethyl)-[1,3,5]triazine-2,4,6-triamine ( trizbenzim) and its Cu and Zn complexes (Cu-trizbenzim, Zn-trizbenzim) were synthesized and characterized by IR, NMR, and MALDI-TOF techniques. The pure ligand and its complexes interacted with human telomere DNA sequence d(TTAGGG), HTelo8and HTelo20and the interactions were followed by circular dichroism spectroscopy, FID assay, and molecular docking techniques. The compounds were tested for anticancer activity towards selected cell lines. All the three compounds stabilized the HTelo8 and HTelo20 in parallel and antiparallel G-quadruplex conformations with salt conditions. Under no-salt conditions, the compounds induce and stabilize the G-quadruplex conformation in antiparallel topology selectively. The pure ligand, Cu-trizbenzim, and Zn-trizbenzim were involved in partial or classical intercalation and some backbone interactions on the strand. The FID assay using thiazole orange intercalator supports the proposed intercalation mode of binding for the three compounds, especially for the pure ligand and the Cu-complex. The MOE docking experiments using X-ray and NMR derived G-quadruplex models with the title compounds extensively support the G-quadruplex induction and stabilization of the telomere sequence by these compounds. The guanines bases involved in the G-tetrad formation interact well with the triazine and the benzimidazole part of the ligand through strong π-π interactions. The primary mode of binding is described as end stacking and intercalation of the compounds to the G-quadruplex structures. The Cu-trizbenzim exhibited more anticancer property in comparison to the pure ligand and the Zntrizbenzim complex. The IC50 values were in the nanomolar range from 50 to 150nM in concentration. This novel self-induction of G-quadruplex is novel without the presence of alkali metal ions.

Controlled Fluorescence Enhancement of DNA-Binding Dye Through Chain Length Match between Oligoguanine and TOTO.

Fluorescent DNA-binding dyes are extensively employed as probe and biosensing in biological detection and imaging. Experiments and theoretical calculations of thiazole orange homodimeric (TOTO) dye binding to a single-strand DNA (ssDNA), poly(dG)n (n = 2, 4, 6, 8), reveal that the n = 6 complex shows about 300-fold stronger fluorescence than n = 2, 4 and a slightly stronger one than n = 8 complexes, which is benefited from the length match between TOTO and poly(dG)6. The machine learning, based on molecular dynamics trajectories, indicates that TOTO is featured by the dihedral angle along its backbone and its end-to-end distance, in which the latter one defines the stretch and hairpin structures of TOTO, respectively. The time-dependent density functional theory calculations on the low-lying excited states show that the stretched TOTO with π-π end-stacking binding mode can bring about strong fluorescence with localized π-π* transitions. For the n = 2, 4, and 8 complexes, the linear scaling quantum mechanics calculations indicate that the dominant hairpin TOTO with intercalative binding modes have relatively larger binding energies, leading to fluorescence quenching by intramolecular charge transfer. Our results may provide an insight for modulating the DNA-dye binding modes to tune the degree of charge transfer and designing fluorescent probes for the recognition of specific DNA sequences.

DNA Binding and DNA Cleavage Activities of Newly Synthesized Co

Two water soluble complexes with CoII and CuII ions were synthesized using a novel β-cyclodextrin based azo-functionalized Schiff base as a ligand. The Schiff base and its metal complexes were characterized by different physico-chemical and spectroscopic methods. From the analyses of the experimental data, distorted octahedral geometry has been assigned for both the metal complexes. The binding interactions between the metal complexes and DNA were investigated by means of a thermal denaturation study and viscosity measurements as well as by electronic absorption and fluorescence spectroscopy. The DNA cleavage efficacy of the metal complexes was also studied by agarose gel electrophoresis using pBR DNA. These studies revealed that both the metal complexes followed an intercalative mode of binding to calf thymus (CT)-DNA and also effectively cleaved the supercoiled pBR DNA. The CoII complex, however, more efficiently cleaved CT-DNA than the CuII complex as much as the experimental results are concerned.

In vitro DNA Binding, Anticancer and Molecular Docking Studies of New Sydnone Compounds

Sydnones have been a novel class of mesoionic compound due to versatility of their applications in various fields. Sydnone derivative have seen as an interesting structure grouped in the heterocyclic community, which is having regions of both positive and negative charges linked with a poly-heteroatomic system. This structural characteristic allows them to cross biological membranes and interact with biomolecules. Four sydnones namely 3-(4-decyloxybiphenyl-4′-yl) sydnone (MC-176), 3-(4-octyloxy-2,3-difluorobiphenyl-4′-yl) sydnone (MC-192), 3-(4-biphenyl-4′-yl) sydnone (MC-450) and 3-(4-butylbiphenyl-4′-yl) sydnone (MC-456) were evaluated for biophysical interactions between DNA and sydnones and antiproliferative activity. The UV-visible spectroscopic study indicates interaction between sydnone and dsDNA with a slight red and hypochromic shift in absorption spectra, which shows the intercalation mode of binding. The binding constant of DNA-Sydnone complexes were in the range from 1.4 × 104 M–1 to 7.1 × 104 M–1 for different sydnone compounds (MC-176, MC-192, MC-450, MC-456). FTIR spectra indicated that sydnone interaction with DNA occurs through base pairs and the phosphate backbone of the DNA. The cytotoxic and apoptotic effects of a sydnone derivatives on human cervical cancer (HeLa) and breast tumor (BT) 474 cancer cell lines were determined. The compounds possess antiproliferative activity in a concentration-dependent mode. The changes of morphological characteristic of cancer cells were determined by fluorescent staining techniques indicate the apoptotic cell death. The molecular docking studies of sydnone compounds with caspase 3 and EGF-TK showed better interactions (according to docking score) along with commercially available breast cancer drug molecule anastrozole. The docking score of sydnone molecules (MC-456, MC-450, MC-192 and MC-176) with EGF-TK enzyme were -6.44, -6.42, -5.46 and -4.53, respectively. The binding energy of anastrozole with EGF-TK was -6.41. As well Caspase 3 inhibition with sydnone compounds MC-456, MC-450, MC-192 and MC-176 were -6.09, -6.48, -5 and -3.49, respectively. The binding energy of anastrozole with caspase 3 was -6.24. All sydnone compounds were studied for ADME toxicity studies along with Lipinski rule of five to assess their drug likeness properties by in silico approach. MC-450 found to have good ADMET (absorption, distribution, metabolism, excretion and toxicology) properties among all the sydnone compounds. Thus, the present work indicates that these sydnone compounds would be a well prospective in developing anticancer medicines.

Synthesis, crystal structures, anticancer activities and molecular docking studies of novel thiazolidinone Cu(II) and Fe(III) complexes targeting lysosomes: special emphasis on their binding to DNA/BSA.

Novel [CuL2Cl]Cl·H2O (1) and [FeL2Cl2]Cl·MeOH·CHCl3·H2O (2) complexes of (Z)-N'-((E)-3-methyl-4-oxothiazolidin-2-ylidene)picolinohydrazonamide (L) as antitumor agents were designed and synthesized in order to explore DNA and serum albumin interaction. X-ray diffraction revealed that both 1 and 2 were a triclinic crystal system with P1̄ space group, which consisted of a positive electric main unit, a negative chloride ion and some solvent molecules. The complexes with DNA and bovine serum albumin (BSA) were studied by fluorescence and electronic absorption spectrometry. The results indicated that there was moderate intercalative binding mode between the complexes and DNA with Kapp values of 2.40 × 105 M-1 (1) and 6.49 × 105 M-1 (2). Agarose gel electrophoresis experiment showed that both 1 and 2 exhibited obvious DNA cleavage activity via an oxidative DNA damage pathway, and the cleavage activities of 1 were stronger than those of 2. Cytotoxicity assay showed that 1 had a more effective antitumor activity than 2. The two complexes were bound to BSA by a high affinity and quenched the fluorescence of BSA through a static mechanism. The thermodynamic parameters suggested that hydrophobic interactions played a key role in the binding process. The binding energy xpscore of 1 and 2 were -10.529 kcal mol-1 and -10.826 kcal mol-1 by docking studies, and this suggested that the binding process was spontaneous. Complex 1 displayed a lysosome-specific targeting behavior with a Pearson coefficient value of 0.82 by confocal laser scanning microscopy (CLSM), and accumulated in the lysosomes, followed by the disruption of lysosomal integrity.

DNA threading intercalation of enantiopure [Ru(phen)2bidppz]2+ induced by hydrophobic catalysis.

The enantiomers of a novel mononuclear ruthenium(ii) complex [Ru(phen)2bidppz]2+ with an elongated dppz moiety were synthesized. Surprisingly, the complex showed no DNA intercalating capability in an aqueous environment. However, by the addition of water-miscible polyethylene glycol ether PEG-400, self-aggregation of the hydrophobic ruthenium(ii) complexes was counter-acted, thus strongly promoting the DNA intercalation binding mode. This mild alteration of the environment surrounding the DNA polymer does not damage or alter the DNA structure but instead enables more efficient binding characterization studies of potential DNA binding drugs.

Spectroscopic, anticancer and antioxidant studies of fluxional trans-[PdCl2(S-acylthiourea)2] complexes

A library of palladium(II) acylthiourea complexes (1–6) of the type [PdCl2{C8H13N2OS(R)}2] [where R = C6H4CH3(o) (1), C6H5 (2), C6H4OCH3(p) (3), C6H4OC2H5(p) (4), C10H7 (5) or C6H5Cl(p) (6)] was synthesized and characterized by UV–Visible, FT-IR, 1H NMR, 13C NMR and ESI-Mass spectroscopy, and elemental analysis. Single crystal X-ray structure of complex 4 revealed the monodentate coordination of acylthiourea ligand through sulphur atom to the palladium ion in a trans fashion. In addition, variable-temperature (VT) NMR studies were performed to analyze the fluxional nature of complexes. The interaction of complexes with calf thymus (CT) DNA and BSA (bovine serum albumin) was analyzed by spectroscopic and molecular docking studies. The results inferred intercalation binding mode of the complexes with DNA. All the complexes exhibited good binding with BSA as well. Further, the complexes were found to act as good scavengers of DPPH as deduced from the antioxidant assay. In vitro cytotoxicity of the compounds against A549 (lung) cancer and HEK293 (human embryonic kidney) normal cell lines was investigated by MTT assay. Among the six complexes, complex 5 bearing a napthyl substitution in acylthiourea exhibited a remarkable activity against A549 cell line with an IC50 value of 14.8 µM and was more active than cisplatin (IC50 = 17.8 µM). On the other hand, it showed less toxicity on HEK293 cell line. The cell death mechanism was analyzed by AO/EB and DAPI staining, flow cytometry and Western blot investigations, which revealed that complex 5 could initiate cell death through apoptosis.

DNA-Binding Capabilities and Anticancer Activities of Ruthenium(II) Cymene Complexes with (Poly)cyclic Aromatic Diamine Ligands.

Ruthenium(II) arene complexes of the general formula [RuCl(η6-p-cymene)(diamine)]PF6 (diamine = 1,2-diaminobenzene (1), 2,3-diaminonaphthalene (2), 9,10-diaminophenanthrene (3), 2,3-diaminophenazine (4), and 1,2-diaminoanthraquinone (5) were synthesized. Chloro/aqua exchange was evaluated experimentally for complexes 1 and 2. The exchange process was investigated theoretically for all complexes, revealing relatively fast exchange with no significant influence from the polycyclic aromatic diamines. The calf thymus DNA (CT-DNA) binding of the complexes increased dramatically upon extending the aromatic component of the diamines, as evaluated by changes in absorption spectra upon titration with different concentrations of CT-DNA. An intercalation binding mode was established for the complexes using the increase in the relative viscosity of the CT-DNA following addition of complexes 1 and 2. Theoretical studies showed strong preference for replacement of water by guanine for all the complexes, and relatively strong Ru–Nguanine bonds. The plane of the aromatic systems can assume angles that support non-classical interactions with the DNA and covalent binding, leading to higher binding affinities. The ruthenium arenes illustrated in this study have promising anticancer activities, with the half maximal inhibitory concentration (IC50) values comparable to or better than cisplatin against three cell lines.

Spectroscopic and electrochemical study of interactions between DNA and different salts of 1,4-dihydropyridine AV-153.

1,4-dihydropyridines (1,4-DHP) possess important biochemical and pharmacological properties, including antimutagenic and DNA-binding activity. The latter activity was first described for water-soluble 1,4-DHP with carboxylic group in position 4, the sodium salt of the 1,4-DHP derivative AV-153 among others. Some data show the modification of physicochemical properties and biological activities of organic compounds by metal ions that form the salts. We demonstrated the different affinity to DNA and DNA-protecting capacity of AV-153 salts, depending on the salt-forming ion (Na, K, Li, Rb, Ca, Mg). This study aimed to use different approaches to collate data on the DNA-binding mode of AV-153-Na and five other AV-153 salts. All the AV-153 salts in this study quenched the ethidium bromide and DNA complex fluorescence, which points to an intercalation binding mode. For some of them, the intercalation binding was confirmed using cyclic voltammetry and circular dichroism spectroscopy. It was shown that in vitro all AV-153 salts can interact with four DNA bases. The FTIR spectroscopy data showed the interaction of AV-153 salts with both DNA bases and phosphate groups. A preference for base interaction was observed as the AV-153 salts interacted mostly with G and C bases. However, the highest differences were detected in the spectral region assigned to phosphate groups, which might indicate either conformational changes of DNA molecule (B form to A or H form) or partial denaturation of the molecule. According to the UV/VIS spectroscopy data, the salts also interact with the human telomere repeat, both in guanine quadruplex (G4) and single-stranded form; Na and K salts manifested higher affinity to G4, Li and Rb –to single-stranded DNA.

Unexpected structure of enaminone Pd(II) complex in comparison with Cu(II) complex: Synthesis, characterization, DNA binding and antitumor activity

Novel Pd(II) and Cu(II) complexes have been synthesized by the reaction of Na2PdCl4 and CuCl2·2H2O with fluorinated enaminone ligand leading to the formation of complexes having the formulae [Pd(enm)Cl2] and [Cu2(diCO)4]; where enm and diCO are enaminone and deprotonated dicarbonyl containing ligands, respectively. The structures and geometry of the two metal chelates have been elucidated by applying alternative spectral and analytical tools including elemental analysis, FT-IR spectra, 1H NMR spectra and UV–Vis spectra. The molecular structure of the Cu(II) complex has been determined by single crystal X-ray diffraction; the complex crystalizes in monoclinic P21/c space group. Square pyramidal geometry has been confirmed for Cu(II) complex where Pd(II) complex has the expected square planar geometry. The mechanism of the in-situ conversion of the enaminone to dicarbonyl ligand with CuCl2·2H2O was illustrated. The type of interaction between the two complexes and salmon sperm DNA (SS-DNA) has been studied applying absorption spectra and viscosity measurements. The binding constant values (kb) was calculated to be (1.17 ± 0.6) × 104 and (3.62 ± 0.4) × 104 M−1 for Pd(enm)Cl2 and Cu2(diCO)4, respectively, which confirmed the interaction of the two complexes with DNA via intercalative mode of interaction. Intercalative binding mode between the studied compounds and DNA was further confirmed by the results of viscosity measurements. The anticancer activity of the two metal complexes has been evaluated against breast cancer cell line (MCF-7) and the liver cancer cell line (HepG-2) in comparison with the well-known anticancer drug cis-DDP. Surprisingly, we found that Cu2(diCO)4 complex has activity (IC50 = 3.26 μg/mL) against a human liver cancer cell line (HepG2) exceeding the efficiency of the reference drug cis-DDP (IC50 = 3.67 μg/mL).

Probing the Strength and Mechanism of Binding Between Amifampridine and Calf Thymus DNA.

In this work, we have investigated the strength and mechanism of amifampridine (3,4-Diaminopyridine/3,4-DAP) interaction with calf thymus DNA (ct-DNA). The existence and the strength of interaction are evaluated using circular dichroism (CD), UV-vis absorption, and differential pulse voltammogram studies. Results from UV-vis absorption technique indicate that amifampridine can significantly interact with DNA through a binding constant of Kb = 1.66 × 105 M-1 at 298 K. The mechanism of the interaction between amifampridine and DNA is also studied using ionic effect investigations, competitive fluorescence experiments, viscosity measurements, and molecular docking studies. The viscosity results indicate that amifampridine can bind to DNA via intercalation binding mode. Competitive fluorescence experiments using Acridine Orange (AO) and Hoechst 33258 (HO) probes also reveal that amifampridine binds to DNA via an intercalation mode of binding. Finally, the molecular docking studies also suggest that amifampridine tends to bind with the G-C rich region of DNA.

A DNA Based Biosensor Amplified With ZIF-8/Ionic Liquid Composite for Determination of Mitoxantrone Anticancer Drug: An Experimental/Docking Investigation.

An ultrasensitive DNA electrochemical biosensor based on the carbon paste electrode (CPE) amplified with ZIF-8 and 1-butyl-3-methylimidazolium methanesulfonate (BMIMS) was fabricated in this research. The DNA/BMIMS/ZIF-8/CPE was used for the selective determination of a mitoxantrone anticancer drug in aqueous solution, resulting in a good catalytic effect and a powerful ability for determining mitoxantrone. Also, the interaction of the mitoxantrone anticancer drug with guanine bases of ds-DNA was used as a powerful strategy in the suggested biosensor, which was confirmed with docking investigation. Docking study of mitoxantrone into the ds-DNA sequence showed the intercalative binding mode of mitoxantrone into the nitrogenous-based pairs of ds-DNA. The effective factors such as ds-DNA concentration, temperature, buffer types, and incubation time were also optimized for the fabricated mitoxantrone biosensor. The results showed that, under optimum conditions (T = 25°C; incubation time=12 min; pH= 4.8 acetate buffer solution and [DNA] = 50 mg/L), the DNA/BMIMS/ZIF-8/CPE could be used in mitoxantrone assay in a concentration ranging from 8.0 nM to 110 μM with a detection limit of 3.0 nM. In addition, recovery data between 99.18 and 102.08% were obtained for the determination of mitoxantrone in the injection samples using DNA/ZIF-8/BMIMF/CPE as powerful biosensors.

Comparative binding analysis of noscapine and piperine with tRNA: A structural perturbation and energetic study.

In this study, we have exploring the binding mechanisms of the two anticancer alkaloid noscapine (NOS) and piperine (PIP) with tRNA using different spectroscopy and computational method. Absorbance and emission spectra revealed that both the drugs show strong binding with tRNA, where NOS intercalate between the base pairs of tRNA and PIP binds in the groove of tRNA. Competitive binding study and steady state anisotropy further confirms the intercalative mode of binding between NOS and tRNA and groove binding in PIP-tRNA complex. The observed thermodynamic parameters suggested that NOS-tRNA complex formation is endothermic and entropy driven, however it was exothermic, and enthalpy driven in case of PIP-tRNA complex. CD and time resolved fluorescence studies show the structural perturbations and conformational change in tRNA structure with NOS as well as PIP. Molecular docking studies are comparable with experimental results and further confirmed that the hydrophobic interactions involved in the NOS-tRNA binding, whereas hydrogen binding and van der Waals interactions play important role in the PIP-tRNA complex formation. This study can be useful to understand the potential binding and resultant tRNA damage by alkaloids and deigned new target specific anticancer drug.

Designing a two-stage colorimetric sensing strategy based on citrate reduced gold nanoparticles: Sequential detection of Sanguinarine (anticancer drug) and visual sensing of DNA.

Distance dependent optical properties of colloidal gold nanoparticles offer designing of colorimetric sensing modalities for detection of a variety of analytes. Herein, we report a simple and facile colorimetric detection assay for an anti-cancer drug, Sanguinarine (SNG) and Calf Thymus DNA (Ct-DNA) based on citrate reduced gold nanoparticles (CI-Au NPs). The electrostatic interaction between SNG and CI-Au NPs induce aggregation of Au NPs accompanied with visible colour change of colloidal solution. The assay conditions like salt concentration, pH and reaction time had been adjusted to achieve highly sensitive and fast colorimetric response. Furthermore, the optimized CI-Au NPs/SNG sensing system is used for the detection of Ct-DNA based on the mechanism of anti-aggregation of CI-Au NPs. The simultaneous presence of SNG and Ct-DNA prevent aggregation of Au NPs owing to preferential formation of Ct-DNA-SNG intercalation complex and colour of the Au NPs solution tends to remain red, depending on the concentration of Ct-DNA in solution. The degree of aggregation and anti-aggregation of CI-Au NPs was monitored using Transmission electron microscopic (TEM) measurements and UV-Visible spectrophotometry by analysing the ratio of absorptions for aggregated and dispersed Au NPs. The intercalation mode of binding between SNG and Ct-DNA in CI-Au NPs/SNG sensing system was determined by Fluorescence spectral studies and UV-thermal melting studies. The absorption ratio (A627/A525) of Au NPs exhibited a linear correlation with SNG concentrations in the range from 0 to 0.9μM with detection limit as 0.046μM. This optical method can determine Ct-DNA as low as 0.36μM and the calibration is linear for concentration range 0 to 5μM. The proposed sensing strategy enables detection as well as quantification of SNG & Ct-DNA in real samples with satisfactory results and finds application in drug or DNA monitoring.