Groove Binding Mode Research Articles

Biophysical insights on the interaction of anticoagulant drug dicoumarol with calf thymus-DNA: deciphering the binding mode and binding force with thermodynamics

The biological activity of drugs is exhibited due to their interactions with bio-receptors. Dicoumarol (DIC) is a natural hydroxycoumarin and a well-known anticoagulant. DNA is the genetic material and one of the targets of numerous drugs. The interaction of DIC with calf-thymus DNA (ct-DNA) has been studied using different biophysical techniques and docking studies. The binding constant in the order of 103 to 104 M−1 was observed from spectroscopic studies. Thermodynamic studies at 4 different temperatures revealed the spontaneity of the interaction with the entropy-driven process. Marker displacement studies with competitive markers of intercalators (ethidium bromide) and groove binders (Hoechst 33258) confirmed the groove-binding nature of DIC in DNA. The groove-binding mode of DIC was complemented by different studies like viscosity measurements, DNA melting, and the effect of KI on the binding. A minor perturbation in the DNA viscosity and no significant change in the DNA melting temperature (T m) after binding with DIC further confirms the groove binding mode. The effect of KI on the DIC and DIC-DNA system suggested the absence of DIC intercalation. The absence of significant electrostatic force was revealed from the ionic-strength effect study. Binding-induced conformational variation in ct-DNA was absent in circular dichroism studies. Molecular docking studies suggested the position of DIC within the minor groove of ct-DNA, covering three base pairs long. The outcome of this report may help in understanding the pharmacodynamics and pharmacokinetics of dicoumarol analogs and related molecules. Communicated by Ramaswamy H. Sarma

Cytotoxic activity of Ru(II)/DPEPhos/N,S-mercapto complexes (DPEPhos = bis-[(2-diphenylphosphino)phenyl]ether)

We report here on three new ruthenium(II) complexes, [Ru(DPEPhos)(mtz)(bipy)]PF6 (Ru1), [Ru(DPEPhos)(mmi)(bipy)]PF6 (Ru2) and [Ru(DPEPhos)(dmp)(bipy)]PF6 (Ru3). DPEPhos = bis-[(2-diphenylphosphino)phenyl]ether, mtz = 2-mercapto-2-thiazoline, mmi = 2-mercapto-1-methylimidazole, dmp = 4,6-diamino-2-mercaptopyrimidine and bipy = 2,2′-bipyridine. The compounds were characterized by several spectroscopic techniques, and the molecular structure of Ru1 complex was determined by single-crystal X-ray diffraction. The cytotoxicity of Ru1 – Ru3 complexes were tested against the A549 (human lung) and the MDA-MB-231 (human breast) cancer cell lines and against MRC-5 (non-tumor lung) and MCF-10A (non-tumor breast) cell lines through the MTT assay. All three complexes are cytotoxic against the cell lines studied, with IC50 values lower than those found for the cisplatin. Among them, the Ru2 complex has shown the best selectivity against MDA-MB-231 cancer cell lines, with an IC50 value 12 times lower than that on MCF-10A. The complex Ru2 was capable to induce changes in MDA-MB-231 cells morphology, with loss of cellular adhesion, inhibited colony formation and induce an accumulation of cells at the sub-G1 phase, with an increase in S-phase and decrease of cells at G2 phase. Viscosity, electrochemical and Hoechst 33258 displacement experiments for Ru1 – Ru3 complexes with calf thymus DNA (CT-DNA) showed an electrostatic and groove binding mode of interaction. Additionally, the complexes interact with the protein Human Serum Albumin (HSA) by static mechanism. The negative values for ΔH and ΔS indicate that van der Waals forces and hydrogen bonding may occurs between the complexes and HSA. Therefore, this class of complexes are promising anticancer candidates and may be selected to further detailed studies.

Single crystal structure of nitro terminated Azo Schiff base: DNA binding, antioxidant, enzyme inhibitory and photo-isomerization investigation

Novel azo schiff base compound, namely, 2‑hydroxy-5-[(E)-phenyldiazenyl] benzaldehyde (AzNP) was synthesized by reacting 2‑hydroxy-5-[(E)-phenyldiazenyl]benzaldehyde and 4-(4-nitrophenoxy)benzenamine under inert conditions. The synthesized compound AzNP was characterized by Fourier transform (FT-IR), Nuclear magnetic resonance (NMR) and Ultraviolet-visible (UV–vis) spectroscopy. The solid state structure was elucidated by single-crystal X-ray crystallography. The compound was crystallized in the Monoclinic system with P 1 21/c1 space group, having a = 6.4859(3 Å, b = 15.6673(7) Å, c = 19.7908(9) Å, β = 90.945(2), and Z = 4, showing only one intermolecular C21-H21...N2 interaction, with donor and acceptor distance of 3.5774(16) Å, responsible for the elegant 3D network of the structure. DFT calculations were performed for structure-property relationship information of AzNP. In order to comprehend the selectivity behavior of the compound, binding interaction with CT-DNA was examined using standard optical spectroscopy. The observed hypochromism in the binding studies indicated that ligand substantially interact via the groove binding mode (Kb =9.91×103 mol−1dm3) with the DNA. Further assessment of binding mode of AzNP with DNA was made through hydrodynamic measurement and molecular docking analysis which confirmed the major groove binding mode of the ligand. Additionally, the DPPH (2,2-diphenyl-1-picrylhydrazyl), the ferric reducing power, and the α-amylase inhibition assays were used to evaluate the biological significance. Analysis of Cis-Trans conformational changes was also done to investigate photoisomerization properties of synthesized compound AzNP.

Mechanisms of Surfactin from Bacillus subtilis SF1 against Fusarium foetens: A Novel Pathogen Inducing Potato Wilt.

Fusarium wilt is a severe and worldwide disease in potato cultivation. In this study, Fusarium foetens was first identified as the pathogen of potato wilt. Bacillus subtilis SF1 has the potential for controlling potato wilt induced by F. foetens, resulting in a mycelium growth inhibition of 52.50 ± 2.59% in vitro and a significant decrease in incidence rate by 45.56% in vivo. This research highlighted the antifungal activity of surfactin from B. subtilis SF1 and attempted to reveal the unknown antifungal mechanisms. Surfactin inhibited F. foetens mycelium growth beyond the concentration of 20 μg/μL. Surfactin-treated mycelium appeared to have morphological malformation. Surfactin enhanced reduced glutathione production and caused the increase in values of the extracellular fluids in OD260 and OD280. Surfactin induced differential protein expression and changed the genes' transcription levels. Surfactin binds to fungal DNA via groove-binding mode, with a binding constant of Kb 2.97 × 104 M-1. Moreover, B. subtilis SF1 harbored genes encoding plant-promoting determinants, making potato seedlings grow vigorously. The results will help provide a comprehensive understanding of the mechanisms of surfactin against filamentous fungi and the application of surfactin-producing microbial in the biocontrol of plant pathogenic fungi.

Cu(II) complex of S-benzyl-β-N-(2-methoxybenzylmethylene)dithiocarbazate: Synthesis, DFT calculations, cell cytotoxicity assay and DNA binding studies

A copper(II) complex (CuL2) containing bidentate N,S-donor Schiff base ligands (S-benzyl-β-N-(2-methoxybenzylmethylene) dithiocarbazate, HL) was synthesised and characterised using physicochemical and spectroscopic methods. This work comprehensively includes the single crystal X-ray diffraction analysis of HL, revealing that the centroid of the phenyl ring was engaged in the intermolecular CH interactions that stabilised the three-dimensional (3D) molecular structure. The Hirshfeld surface analysis was used to measure the intermolecular interactions of HL. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations of HL and CuL2 were carried out using B3LYP with the LanL2DZ pseudopotential and 6–311G(d, p) basis set for all the other atoms. The selected calculated frequencies (v(C = N), v(NN), v(C = S)) correlated well with the experimental data obtained, except v(NH). Due to the intra- and intermolecular hydrogen bondings between molecules in solid, some deviation of this band was observed in the calculated gas phase system. The calculated structures and UV–vis results also concur with the experimental findings. It was discovered through cytotoxicity studies that CuL2 had promised good activity against extremely aggressive breast cancer cells (MDA-MB-231). In order to investigate the interactions between cytoactive CuL2 and calf thymus-DNA (DNA), electronic absorption titrations were performed, which revealed moderate binding through groove binding mode with a binding constant (Kb) of 1.75 × 105 M−1. Additionally, the binding capacity of CuL2 with DNA was investigated using molecular docking simulations. The results are comparable with the experimental data, in which CuL2 is bound to the DNA groove via hydrogen bonds and hydrophobic interactions. DNA binding studies have shown that sulfur, nitrogen, and aromatic rings is very important, in terms of the interactions between the lone pairs and π-aromatic ring with nucleobases of DNA.

The biguanide–sulfonamide derivatives: synthesis, characterization and investigation of anticholinesterase inhibitory, antioxidant and DNA/BSA binding properties

A number of new biguanidine-sulfonamide derivatives (1–16) were synthesized and their structures were characterized by spectroscopic and analytical methods. Crystal structures of the compounds 1, 4, 8, 10 and 14 were determined by single crystal X-ray diffraction studies. X-ray crystallographic data showed the π-electron delocalization through the biguanide units. The AChE and BChE cholinesterase inhibitor, DPPH antioxidant and DNA/BSA binding properties of the synthesized compounds were evaluated. Results of cholinesterase inhibitory properties have shown that the compounds containing electron-withdrawing (–F, –Cl) groups have higher AChE/BChE inhibitory and antioxidant activities. Compound 3 showed higher BChE inhibitory activity than tacrine with IC50 value of 28.4 µM. The compounds interact with DNA via minor groove binding mode. The compounds with a naphthyl group in its structure strongly binds with DNA/BSA biomolecules. Communicated by Ramaswamy H. Sarma

The interaction mechanism of candidone with calf thymus DNA: A multi-spectroscopic and MD simulation study

In this investigation, the effects of candidone on the structure and conformation of DNA were evaluated by spectroscopic methods, molecular dynamics simulation, and molecular docking studies. Fluorescence emission peaks, ultraviolet-visible spectra, and molecular docking exhibited the complex formation between candidone and DNA in a groove-binding mode. Fluorescence spectroscopy results also showed a static quenching mechanism of DNA in the presence of candidone. Moreover, thermodynamic parameters demonstrated that candidone spontaneously bound to DNA with a high binding affinity. The hydrophobic interactions were the dominant forces over the binding process. Based on the Fourier transform infrared data candidone tended to attach to the A-T base pairs of the minor grooves of DNA. The thermal denaturation and circular dichroism measurements displayed that candidone caused a slight change in the DNA structure, which was confirmed by the molecular dynamics simulation results. According to the obtained findings from the molecular dynamic simulation, the structural flexibility and dynamics of DNA were altered to a more extended structure.

Molecular Dynamics and Multi-Spectroscopic of the Interaction Behavior between Bladder Cancer Cells and Calf Thymus DNA with Rebeccamycin: Apoptosis through the Down Regulation of PI3K/AKT Signaling Pathway.

The interaction of Rebeccamycin with calf thymus (ctDNA) in the absence and presence of H1 was investigated by molecular dynamics, multi-spectroscopic, and cellular techniques. According to fluorescence and circular dichroism spectroscopies, Rebeccamycin interacted with ctDNA in the absence of H1 through intercalator or binding modes, while the presence of H1 resulted in revealing theintercalator, as the dominant role, and groove binding modes of ctDNA-Rebeccamycin complex. The binding constants, which were calculated to be 1.22 × 104M-1 and 7.92 × 105M-1 in the absence and presence of H1, respectively, denoted the strong binding of Rebeccamycin with ctDNA. The binding constants of Rebeccamycin with ct DNA in the absence and presence of H1 were calculated at 298, 303 and 308K. Considering the thermodynamic parameters (ΔH0 and ΔS0), both vander waals forces and hydrogen bonds played predominant roles throughout the binding of Rebeccamycin to ctDNA in the absence and presence of H1. The outcomes of circular dichroism suggested the lack of any major conformational changes in ctDNA upon interacting with Rebeccamycin, except some perturbations in native B-DNA at local level. Additionally, the effect of NaCl and KI on ctDNA-Rebeccamycin complex provided further evidence for the reliance of their interaction modes on substituted groups. The observed increase in the relative viscosity of ctDNA caused by the enhancement of Rebeccamycin confirmed their intercalation and groove binding modes in the absence and presence of H1. Moreover, the assessments of molecular docking simulation corroborated these experimental results and also elucidated the effectiveness of Rebeccamycinin inhibiting and proliferating T24 and 5637 cells. Meanwhile, the ability of Rebeccamycin in inhibiting cell proliferation and tumor growth through the induction of apoptosis by down regulating the PI3K/AKT signaling pathway were provided.

Synthesis, spectral characterization of pyrazole derived Schiff base analogs: molecular dynamic simulation, antibacterial and DNA binding studies

We have synthesized the pyrazole-bearing Schiff base derivatives (5a–5e) and (6a–6h) then the structural confirmation was supported by various spectral analyses. The antibacterial activity of all analogs was screened against bacterial strains Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Escherichia coli, Klebsiella pneumonieae and Pseudomonas aeruginosa. In comparison to the reference drug ciprofloxacin, the lead analogs 5c and 6c showed potent activity, with MIC values of 64 µg/mL against E. coli and B. subtilis. Compound 5c showed a moderate effect with a MIC value of 128 µg/mL against B. subtilis, P. aeruginosa and K. pneumonieae, while compound 6c was against E. coli and P. aeruginosa. Furthermore, the compounds 5c and 6c displayed groove binding mode towards CT-DNA by absorption, emission, competitive fluorescence studies using EtBr, CD and time-resolved fluorescence studies. Thermodynamic parameters of analogs 5c and 6c with CT-DNA were also calculated at 298, 303 and 308K temperatures by UV–visible spectroscopy. The molecular docking studies give the docking score for all compounds with PDB codes: 1BNA and 2XCT. The MD simulation study of analogs 5c and 6c was also carried out. The pharmacokinetic and ADME properties were calculated for all of the synthesized analogs (5a–5e) and (6a–6h).Communicated by Ramaswamy H. Sarma

Ruthenium(II) Complexes Coupled by Erianin Via a Flexible Carbon Chain as a Potential Stabilizer of c-myc G-Quadruplex DNA

Herein, two novel ruthenium(II) complexes coupled by erianin via a flexible carbon chain, [Ru(phen)2(L1-(CH2)4-erianin)](ClO4)2 (L1 = 2-(2-(tri-fluoromethyphenyl))-imidazo [4,5f][1-10]phenanthroline (1) and [Ru(phen)2(L2-(CH2)4-eria)](ClO4)2 (L2 = 2-(4-(tri-fluoromethyphenyl))-imidazo [4,5f][1,10]phenanthroline (2), have been synthesized and investigated as a potential G-quadruplex(G4) DNA stabilizer. Both complexes, especially 2, can bind to c-myc G4 DNA with high affinity by electronic spectra, and the binding constant calculated for 1 and 2 is about 15.1 and 2.05 × 107 M-1, respectively. This was further confirmed by the increase in fluorescence intensity for both complexes. Moreover, the positive band at 265 nm in the CD spectra of c-myc G4 DNA decreased treated with 2, indicating that 2 may bind to c-myc G4 DNA through extern groove binding mode. Furthermore, fluorescence resonance energy transfer (FRET) assay indicated that the melting point of c-myc G4 DNA treated with 1 and 2 increased 15.5 and 16.5 °C, respectively. Finally, molecular docking showed that 1 can bind to c-myc G4 DNA in the extern groove formed by base pairs G7-G9 and G22-A24, and 2 inserts into the small groove of c-myc G4 DNA formed by base pairs T19-A24. In summary, these ruthenium(II) complexes, especially 2, can be developed as potential c-myc G4 DNA stabilizers and will be exploited as potential anticancer agents in the future.

Surface modification of a screen-printed electrode with a flower-like nanostructure to fabricate a guanine DNA-based electrochemical biosensor to determine the anticancer drug pemigatinib.

The present study developed a DNA biosensor to determine pemigatinib for the first time. Three-dimensional carnation flower-like Eu3+:β-MnO2 nanostructures (3D CF-L Eu3+:β-MnO2 NSs) and a screen-printed electrode (SPE) modified with polyaniline (PA) were employed. The double-stranded DNA was also immobilized completely on the PA/3D CF-L Eu3+:β-MnO2 NSs/SPE. Then, electrochemical techniques were used for characterizing the modified electrode. After that, the interaction between pemigatinib and DNA was shown by a reduction in the oxidation current of guanine using differential pulse voltammetry (DPV). According to the analysis, the dynamic range of pemigatinib was between 0.001 and 180.0 μM, indicating the new electrode has a low limit of detection (LOD = 0.23 nM) for pemigatinib. Afterwards, pemigatinib in real samples was measured using the PA/3D CF-L Eu3+:β-MnO2 NSs/SPE loaded with ds-DNA. The proposed DNA biosensor showed good selectivity toward pemigatinib in the presence of other interference analytes, such as other ions, structurally related pharmaceuticals, and plasma proteins. In addition, the interaction site of pemigatinib with DNA was predicted by molecular docking, which showed the interaction of pemigatinib with the guanine bases of DNA through a groove binding mode. Finally, we employed the t-test to verify the capability of the ds-DNA/PA/3D CF-L Eu3+:β-MnO2 NSs/SPE for analyzing pemigatinib in real samples.

Elucidation of the interaction of apocarotenoids with calf thymus DNA by biophysical techniques and in vitro study in MCF-7 cells to explore their potential in cancer therapy.

DNA is one of the targets of cancer-therapeutic small molecules. Cisplatin, a DNA intercalator, is one of the first-line drugs in the cancer chemo regimen which comes with health-compromising side effects during chemotherapy. The synergistic effect of natural molecules with cisplatin can help to potentiate its anti-cancer efficacy and decrease its negative effect on health. Here, we report the interaction of cisplatin with calf thymus-DNA (ct-DNA) in combination with natural molecules like apocarotenoids which are reported for their therapeutic properties. The combinatorial effect of apocarotenoids on ct-DNA was explored through various biophysical techniques such as UV-Visible spectroscopy, circular dichroism studies, DNA melt curve analysis, viscosity measurements, and an in vitro study in MCF-7 cells by cell cycle analysis. UV-Visible spectroscopy studies suggest apocarotenoids and their combination shows a non-intercalative mode of binding. Circular dichroism analysis showed no major changes in DNA form during the interaction of DNA with apocarotenoids and their respective combinations with cisplatin, which is suggestive of the groove-binding mode of apocarotenoids. DNA melt curve analysis showed a decrease in the intensity of the fluorescence for apocarotenoids with cisplatin which indicates the possibility of DNA interaction through groove binding. Viscosity studies suggested a groove binding mode of interaction of ct-DNA with apocarotenoids and their combination as there was minimal change in the viscosity measurements. The in vitro analysis exhibits that the apocarotenoids and their combination have a considerable effect on DNA synthesis. This study provides a better perspective on the possible mode of interaction between ct-DNA and natural molecules along with cisplatin.

Synthesis, Structural Characterization and Investigation of DNA/BSA Binding Properties of a Homo-disulphide Schiff Base Compound Carrying Oxo Propargyl Group

In this work, a new homo-disulphide Schiff base compound (HDSB) was prepared and its structure was characterised by common spectroscopic and analytical methods. The compound was obatined from the condensation reaction of 2-aminothiophenol and 2-hydroxy-4-(prop-2-yn-1-yloxy)benzaldehyde in benzene. In the reaction, both Schiff base condensation and oxidation of thiols into disulphide formed. The isolated compound was structurally characterized by single crystal X-ray diffraction experiment. The homo-disulphide Schiff base compound (HDSB) was screened for its DNA/BSA binding properties using UV-Vis absorption and emission spectral studies. The compound showed considerable binding affinity to double-stranded fish sperm DNA (FSds-DNA) with binding constant of 4.1 × 104 M-1. Spectral measurements suggest that HDSB interacts with DNA in a minor groove binding mode. The compound also showed binding properties towards BSA (bovine serum albumin). The incremental addition of HDSB to the BSA solution resulted in a significant decrease in the characteristic emission band of BSA in the range of 320-500 nm (λexc: 280 nm) showing the binding interactions between HDSB and BSA.

Cu(I)-benzimidazole complexes with triphenylphosphine as coligand: DNA lesion and reactive oxygen-dependent mitochondrial dysfunction inducing apoptosis

Two binuclear Cu(I) complexes [Cu2(L1)(PPh3)2I2] (1) and [Cu2(L2)(PPh3)2Br2] (2) derived from the ligands 1,4-bis((5-bromo-2-(pyridin-2-yl)-1H-benzoimidazol-1-yl)methyl)benzene (L1) and 1,4-bis((2-(pyrazin-2-yl)-1H-benzoimidazol-1-yl)methyl)benzene (L2) were prepared and characterized in this study. Both complexes were found to bind to CT-DNA in a groove-binding mode via spectroscopic studies and molecular docking, and cleave pBR322 DNA efficiently in the presence of H2O2. In vitro antitumor activity test revealed that both complexes exhibited effective anti-proliferative activities against four human cancer cell lines (HCT116, HeLa, SMMC7721, and TFK-1), and that SMMC7721 cells were the most sensitive to complex 1, which is consistent with the finding that the cell uptake of complex 1 is superior to that of complex 2. In SMMC7721 cells, complex 1 mainly accumulated in the nuclei, arrested the cell cycle at the G2/M phase, and caused severe DNA fragmentation. Concomitantly, the generation of reactive oxygen species (ROS) elicited by complex 1 is probably involved in arising mitochondrial dysfunction and apoptosis.

Mechanism of interactions of dsDNA binding with quercetin and its two novel sulfonate derivatives using multispectroscopic, voltammetric, and molecular docking studies

Flavonoids have an important place in chemistry and pharmacology. Several flavonoids, especially Quercetin, have the potential to form molecular complexes with nucleic acid structure and have recently attracted attention due to their prospective clinical and pharmacological uses. DNA is the main target for a wide variety of therapeutic agents. Therefore, there is great interest in studies of binding small molecules with DNA. The interaction of small molecules with DNA provides a structural guide in rational drug design and the synthesis of new and improved drugs with enhanced selective activity and higher clinical efficacy. Even if newly synthesized candidate drug molecules with small molecular weight are capable of indirectly interacting with DNA, the mechanisms that accomplish this need to be clearly known. In this study, the mechanism of fish sperm double strain deoxyribonucleic acid (dsDNA) binding with Quercetin (QCR) and its two novel sulfonate derivatives (quercetin mesylate (QMS) and quercetin tosylate-A (QTS-A)) were researched. For investigating the interaction between the molecules and dsDNA was studied by analytical (spectrophotometric, viscosimetric, and electrochemical) methods. The interaction of dsDNA and two quercetin sulfonate derivatives were compared with the interaction of the QCR standard after all experimental studies. Moreover, the DNA binding constants Kb were determined using each method. The Kb constants calculated for QCR, QMS, and QTS-A are in harmony for all techniques. The results showed that QCR binds to dsDNA via intercalation mode, while QMS and QTS-A bind through minor groove binding mode. In addition to experimental studies, theoretical studies were conducted at room temperature under physiological conditions (pH 7.4). Molecular docking calculations and molecular dynamics (MD) simulations have been found to be compatible with experimental studies.

Electrochemical Studies of the Interaction of Phospholipid Nanoparticles with dsDNA

The effect of phospholipid nanoparticles with different contents of phosphatidylcholine (PhNP80 and PhNP100) on dsDNA was studied by means of the electrochemical method. Changes in the electrochemical behavior of heterocyclic bases guanine, adenine and thymine in the range of potentials of 0.2–1.2 V in the presence of PhNPs were used for the assessment of the binding mechanism of the ligand–DNA interaction. Comparative analysis of the effect of PhNPs with different contents of phosphatidylcholine showed a more pronounced effect on the dsDNA of the PhNP100 nanosystem. From the obtained experimental data on the decrease in the amplitude of the nucleobases’ electrochemical oxidation currents, the electrochemical coefficient of the toxic effect was calculated as the ratio of the electrooxidation currents of dsDNA and dsDNA in the presence of phospholipid nanoparticles. PhNP80/100 (up to 11.4 mg/mL) does not influence dsDNA, PhNP80/100 (14.3–28.5 mg/mL) has a moderate toxic effect on dsDNA, PhNP80/100 at concentrations above 28.5 mg/mL already have a toxic effect, significantly reducing the maximum amplitude of the heterocyclic bases’ electrochemical oxidation current. Peak potentials of electrochemical oxidation of nucleobases did not shift in the presence of PhNP80 and PhNP100 (in the concentration range of 2.3–42.2 mg/mL), which could be possible through a groove-binding mode of phospholipid nanoparticle interaction with dsDNA.

Mixed ligand octahedral Zn(II) complex of N^N^O donor tridentate Schiff base ligand and N^N donor bidentate bipyridine ligand: Synthesis, characterization, biological activity and cytotoxicity

AbstractTridentate NNO donor Schiff base ligand and its mixed ligand zinc(II) complex were synthesized stoichiometrically and characterized by electronic, infrared, mass spectral techniques and elemental analysis. To understand the DNA binding ability, the complex was investigated by various analytical and spectroscopic techniques in presence of calf thymus DNA (CT‐DNA). The binding studies showed that the zinc complex interacts with DNA by groove binding mode with intrinsic binding strength of 2.11 × 105 M−1 and with bovine serum albumin the complex showed dynamic quenching attributed for changes in the secondary structure of BSA with efficient interaction. The MCF‐7 cell line studies of the zinc(II) complex with 90.8 μM IC50 value revealed that the complex is effective for the breast cancer cell line and has a potential as anticancer drug. Furthermore, the tridentate ligand and its mixed ligand zinc complex were screened for antibacterial and antifungal activities, which showed better antimicrobial activity for complex.

Synthesis and Characterisation of Novel Tetra dentate Schiff base Complexes: Biological Evaluation Exploring Anticancer Activity towards MCF 7 Cell Breast Cancer lines with in vitro Docking Studies

A method to synthesize novel tetra dentate ligand and a new series of metal complexes comprising Co (II), Fe (II), Cu (II) and Zn (II) (1-4) were synthesized using 3,5-dichlorosalicylaldehyde and trans 1,2-di aminocyclohexane is described. The structural features and mode of bonding exhibited by Schiff base have been characterized by spectral methods like UV-Vis, FT-IR and ESI-MS. Schiff base ligand and (1-4) complexes displayed superior antibacterial towards both Gram positive and Gram negative bacteria. As well, the antioxidant studies reveal that significant free radical scavenging activity towards the free radical DPPH. Theoretical molecular docking studies to elucidate the interactions of synthesized compounds with biomolecules, a model illustrating specific DNA-binding of synthesized compounds and groove binding mode of DNA interaction was evolved. Cu(II) complex (3) with more pronounced biological activity (antibacterial and antioxidant) was subjected to Cytotoxicity studies against MCF-7 breast cancer cell lines through MMT assay. Cu (II) complex exhibited stronger anti-cancer activity in comparision to ligand in that way the synergistic effects of signifying Cu Schiff base complexes illustrating the higher inhibiting efficiency of 77.2% at 320µg/mL. The proposed study, therefore discloses potentiality of the synthesized new Schiff base derived complexes as a prodrug for cancer treatment.

Multi-spectroscopic, thermodynamic, and molecular docking/dynamic approaches for characterization of the binding interaction between calf thymus DNA and palbociclib

Studying the binding interaction between biological macromolecules and small molecules has formed the core of different research aspects. The interaction of palbociclib with calf thymus DNA at simulated physiological conditions (pH 7.4) was studied using different approaches, including spectrophotometry, spectrofluorimetry, FT-IR spectroscopy, viscosity measurements, ionic strength measurements, thermodynamic, molecular dynamic simulation, and docking studies. The obtained findings showed an apparent binding interaction between palbociclib and calf thymus DNA. Groove binding mode was confirmed from the findings of competitive binding studies with ethidium bromide or rhodamine B, UV–Vis spectrophotometry, and viscosity assessment. The binding constant (Kb) at 298 K calculated from the Benesi–Hildebrand equation was found to be 6.42 × 103 M−1. The enthalpy and entropy changes (∆H0 and ∆S0) were − 33.09 kJ mol−1 and 61.78 J mol−1 K−1, respectively, showing that hydrophobic and hydrogen bonds constitute the primary binding forces. As indicated by the molecular docking results, palbociclib fits into the AT-rich region of the B-DNA minor groove with four base pairs long binding site. The dynamic performance and stability of the formed complex were also evaluated using molecular dynamic simulation studies. The in vitro study of the intermolecular binding interaction of palbociclib with calf thymus DNA could guide future clinical and pharmacological studies for the rational drug scheming with enhanced or more selective activity and greater efficacy.

Imperative persistent interaction analysis of anticancer noscapine-ionic liquid with calf thymus DNA

In this study, we have shown the interaction between opium poppy alkaloid noscapine-based ionic liquid [Pip-Nos]OTf and ct-DNA using UV–visible absorption spectroscopy, fluorescence spectroscopy, CD, and computational studies. The absorption spectra showed a hypochromic shift with no shift in the absorption maxima suggesting groove or electrostatic binding. Fluorescence spectra showed an enhancement in fluorescence emission suggesting that the probable mode of binding should be groove binding. Ethidium bromide (EB) competitive and Ionic strength study showed the absence of intercalative and electrostatic modes of interaction. Further, CD analysis of ct-DNA suggested a groove binding mode of interaction of [Pip-Nos]OTf with ct-DNA. [Pip-Nos]OTf displayed a strong binding with the target ct-DNA with a molecular docking score of −41.47 kJ/mol with all 3D coordinates and full conformation. Also, molecular binding contact analyses depicted the stable binding of drug and ct-DNA with potential hydrogen bonds and hydrophobic interactions. The structural superimposition dynamics analysis showed the stable binding of [Pip-Nos]OTf with the ct-DNA model through RMSD statistics. Moreover, the ligand interaction calculations revealed the involvement of large binding energy along with a high static number of molecular forces including the hydrogen bonds and hydrophobic interactions in their complexation. These significant results report the potency of [Pip-Nos]OTf and its important futuristic role in cancer therapeutics.