DNA Binding Studies Research Articles

Designing of amiloride loaded citrate functionalized amorphous silica nanoparticles to investigate its genotoxic and cytotoxic potential

In the present work, silica-based nanocarrier for the anticancer drug, amiloride have been synthesized and characterized using various physicochemical techniques. The aim of this work emphasis on investigating the physicochemical properties and cytotoxic effects of citrate-functionalized amiloride loaded silica nanoparticles. Silica nanoparticles synthesis was carried out via condensation reaction, then coated by tris sodium citrate, followed by their functionalization using amiloride through EDC-NHS reaction. SEM and HR-XRD analysis indicated the formation of amorphous spherical silica nanoparticles. The existence of citrate coating was evident from FT-IR and TGA results, which were supported by DLS and zeta potential studies. The formation of amiloride conjugated citrate coated silica nanoparticles (SiNPs-Cit@Ami) was confirmed by the DLS, Zeta potential and UV-Visible spectroscopy. Size of SiNPs-Cit@Ami nanoparticles was found to be around 80nm using TEM. Additionally, these nanoparticles showed high loading efficiency and time-dependent release of amiloride. DNA binding studies were examined using UV–Visible, Fluorescence spectroscopic and Competitive fluorescence studies. The results indicate that SiNPs-Cit@Ami bind to Ct-DNA via minor groove binding mode. Furthermore, the cytotoxic effect of SiNPs-Cit@Ami on HepG2 cell lines was found to be higher than amiloride alone. Our findings suggest that SiNPs-Cit@Ami can be employed as a promising candidate for cancer mitigation.

Computational and In vitro Elucidation of Indolenine-barbituric Acid Zwitterions as Potential Chemotherapeutical Agents

Introduction: The continuous pursuit of novel chemotherapeutical agents with improved efficacy and reduced adverse effects remains a critical area of research despite advancements in chemotherapy. We have previously synthesized indolenine and barbituric acid zwitterion scaffolds 1–10 sustainably; however, their precise chemotherapeutical properties are still lacking. Methods: In this present work, we conducted in silico ADMET analyses, molecular docking calculations, DNA binding studies, and cytotoxicity assays on these zwitterions. Results and Discussion: Among the 10 zwitterions, zwitterion 3 bearing a methoxy group demonstrated the highest drug-likeness score, low toxicity, as well as no violation of Lipinski’s rule of five and Veber’s rule. Both molecular docking calculations and DNA binding studies suggested that the minor groove of DNA is the most probable molecular target of 3 among the others (i.e., topoisomerase and tubulin). In addition, zwitterion 3 exhibited selective cytotoxicity against a wide array of human cancer cell lines without noticeable effect against the normal human colon fibroblast CCD- 18Co. Conclusion: Overall, these preliminary findings from our combined computational and experimental strategy suggested that 3 remains promising for further elaboration as a chemotherapeutic agent.

Novel s-triazine derivatives as potential anticancer agents: Synthesis, DFT, DNA binding, molecular docking, MD simulation and in silico ADMET profiling

The ongoing challenge of cancer in modern medicine highlights the urgent need for targeted therapeutic strategies, particularly against the EGFR/PI3K/AKT/mTOR signalling pathways, which are pivotal in tumorigenesis. This study presents the design, synthesis, characterization, DNA binding studies and computational evaluation of a novel series of trisubstituted s-triazine derivatives 3a–n as potential anticancer agents. The synthetic methodology utilized the reaction of various oxygen-containing nucleophiles with cyanuric chloride via nucleophilic aromatic substitution, yielding the corresponding target products with high yield and purity. Density Functional Theory (DFT) calculations utilizing the B3LYP level provided insights into the electronic properties of the compounds, with derivatives 3f, 3n, and 3l displaying the lowest energy gaps and highest electrophilicity indices, indicative of their enhanced reactivity. DNA binding results from UV–Vis absorption spectroscopy confirmed the groove mode of binding for the most potent compound 3f with the binding constant (Kb) value of 6.75 × 104 M−1. Molecular docking studies against DNA (PDB ID: 3EY0) and EGFR (PDB ID: 6V6O) revealed strong binding affinities, with compound 3f (R1= ethoxy, R2= 3-CF3) exhibiting a notable binding energy of -8.9 kcal/mol and −9.1 kcal/mol respectively. Additionally, these compounds showed significant binding interactions with PI3K (PDB ID: 5HJB) and mTOR (PDB ID: 4JSV), suggesting their potential as dual inhibitors of the PI3K/AKT/mTOR pathway. The drug-likeness and ADMET profiles further support the therapeutic promise of compound 3f bearing a 3-trifluoromethyl substituent.

Synthesis, antimicrobial, DNA binding, and computational studies of some bis- and poly(4-methyl-2H-chromen-2-one) derivatives

Synthesis, antimicrobial, DNA binding, and computational studies of some bis- and poly(4-methyl-2H-chromen-2-one) derivatives

Charge Transfer Interaction Dynamics between 2-Methyl-8-hydroxyquinoline and 2,4-Dinitrophenol: Synthesis, Spectroscopic Characterization, DNA Binding and DFT Studies

A novel charge transfer (CT) complex was formed by combining the electron-acceptor 2,4-dinitrophenol (DNP) with the electron-donor 2-methyl-8-hydroxyquinoline (MHQ). The complex obtained was further characterized using both experimental and theoretical methods. The Benesi-Hildebrand equation can be utilized to determine various spectroscopic physical measurements such as the molar absorptivity (εCT) and formation constant (KCT). The CT complex has a stoichiometry of 1:1. Multiple spectroscopic methods were employed to investigate the resultant solid compound. The existence of charge and proton transfer in the resultant complex was confirmed by FT-IR, 1H NMR, SEM-EDX and powder-XRD studies. An electron absorption spectroscopy examination was done to analyze the complex DNA binding capability. The resulting complex was determined to have an intercalative binding mechanism, with an intrinsic binding constant (Kb) value of 4.2 × 106 M-1. The experimental results were corroborated by performing theoretical calculations using DFT using a CAM-B3LYP/6-31G(d,p) basis set. The geometrical parameters, electrostatic potential maps (MEPs) and Mullikan charges were computed and examined in agreement with the experimental observations. In addition to electron transmission, the stability of the complex is influenced by the presence of a hydrogen bond.

Evaluation of Antimicrobial, Antitumor, Antioxidant Activities, and Molecular Docking Studies of Some Co(II), Cu(II), Mn(II), Ni(II), Pd(II), and Pt(II) Complexes With a Schiff Base Derived From 2‐Chloro‐5‐(trifluoromethyl)aniline

ABSTRACTThe antimicrobial, antitumor and antioxidant potential of Co(II), Cu(II), Mn(II), Ni(II), Pd(II), and Pt(II) complexes with 2‐(((2‐chloro‐5‐(trifluoromethyl)phenyl)imino)methyl)phenol HL ligand was investigated. A molecular docking study was carried out to estimate the predicted binding affinity of the compounds to protein targets involved in proliferative and bacterial activities. Fluorescence quenching studies and synchronous spectra were used to examine the metal complexes interactions with CT‐DNA and BSA protein. The DNA binding study have revealed that the complexes are capable of binding with DNA via intercalative mode. The antimicrobial activity of the ligand and metal complexes was studied against three Gram‐positive bacteria, two Gram‐negative bacteria, and three strains of fungi. The best antibacterial effect was demonstrated by the Pt(II) complex on the Staphylococcus aureus strain, and as for the inhibitory effect on fungi, it was stronger on the Candida albicans strain after treatment with the Co(II) complex. The in vitro antiproliferative activity of ligand and complexes was analyzed using MTT, Annexin V/PI, and cell cycle assays. The in vitro results showed that, except for Pd(II) complex, where slight effects were observed, the MCF‐7 line was resistant to the activity of the complexes. In the case of A549 cells, Cu(II) and Pd(II) complexes showed a dose‐dependent antitumor activity, confirmed by both the Alamar blue and the Annexin V/PI analysis. Finally, the antioxidant activity of the compounds was examined by ABTS and DPPH methods. Antioxidant investigation showed that the Ni(II) complex possesses a remarkable ability to trap the cation of the ABTS+ radical (IC50 value 9.35 μM).

Co(II), Ni(II), and Cu(II) Ternary Complexes With 2,6‐Pyridinedicarboxylic Acid and 2,2′‐Bipyridyl: Synthesis, Characterization, DNA Binding, Photo‐Cleavage, and Antimicrobial Studies

ABSTRACTThe interaction of 2,6‐pyridinedicarboxylicacid (PDA) and 2,2′‐bipyridyl (Bipy) with Co(II), Ni(II), and Cu(II) ions produced new ternary complexes [M (PDA)(Bipy)(H2O)] (M = Co(II), Ni(II), and Cu(II)), which were studied by elemental, spectral (FT‐IR, Mass, UV–Vis), and thermal analysis, and their interaction with Ct‐DNA was thoroughly studied using various methods, including absorption spectroscopy, fluorescence spectroscopy, and viscosity measurements. Spectrophotometric titration and viscosity measurements indicated that all the complexes bind to DNA via the groove mode of binding. The salt‐dependent binding of ternary metal complexes to Ct‐DNA has been studied by a UV–Vis spectrophotometric titration experiment. Furthermore, photocleavage studies were used to examine how the metal complexes interacted with the pBR322 DNA, and the results proved that these compounds have obvious photo cleavage properties. The biological effects were studied by antibacterial activity.

Naphthalene Diimide and Bis-Heteroleptic Ru(II) Complex-Based Hybrid Molecule with 3-in-1 Functionalities.

Multipurpose applications of a newly developed homobimetallic Ru(II) complex, Ru-NDI[PF6]4, which incorporates 1,10-phenanthroline and triazole-pyridine ligands and linked via a (-CH2-)3 spacer to the reputed anion-π interacting NDI system, are described. Solution-state studies of the bimetallic complex, including EPR, PL, UV-vis, and NMR experiments, reveal two sequential one-electron transfers to the NDI unit, generating NDI⋅- and NDI2- in the presence of F- selectively. This process inhibits the primary electron transfer from Ru(II) to the NDI unit, thereby allowing the 3MLCT-based emission of the complex to be recovered, resulting in a corresponding ten-fold increase in luminescence intensity. DFT and TD-DFT computational studies further elucidate the experimentally observed absorption spectra of the complex. Secondly, CT-DNA binding studies with the complex are performed using various spectroscopic analyses such as UV-vis, PL, and CD. Comparative DNA binding studies employing EB and molecular docking reveal that the binding with CT-DNA occurs through both intercalative and groove binding modalities. Thirdly, the photocatalytic activities of the complex towards C-C, C-N, and C-O bond formation in organic cross-coupling reactions, including the amidation of α-keto acids to amines and the oxidation of alcohol to aldehydes, are also demonstrated.

Novel Co2+ and Cd2+ Complexes Derived From a New N‐Donor Pyridyl‐Functionalized Thiophosphoric Triamide Ligand: Structural Investigation, DNA/COVID‐19/Monkeypox Molecular Docking, and Biological Assays

ABSTRACTA thiophosphoric triamide (SPT) ligand P(S)[NH‐2Py]3 was synthesized and utilized as a ligand to make novel binuclear and mononuclear Co2+ and Cd2+ complexes. The compounds are the first examples of discrete chelate SPT complexes with a [N]3P(S)‐based backbone in which the SPT acts as a flexible tridentate N,N,N‐donor or N,N,O‐donor ligand. The metal cation features a hexacoordinate environment M(N)3(Cl)3/M(N)4(O)2 adopting a distorted octahedral geometry. Hirshfeld surface analysis affirms that the pyridinyl nitrogen is a more dominant H‐bond acceptor than the thiophosphoryl sulfur atom. The inhibitory activity against the MDA‐MB‐231 cancer cell line in vitro indicated a good inhibitory effect for all compounds. The mononuclear Co2+ complex showed a stronger inhibitory activity against cancer cells than other studied compounds with an IC50 of 62 ± 1.4 nM. Antioxidant and antihemolytic activity of the compounds showed appreciable performance with the highest activities for the Cd2+ complex. A computational DNA binding study by molecular docking indicated a good affinity of the compounds with the DNA receptor by a mixed mode of interactions. Docking was also performed on SARS‐CoV‐2 and monkeypox (Mpox), resulting in binding energies (−5.5 to −8.9 kcal/mol) that are competitive with current effective drugs.

Investigation of cytotoxic indoleninyl-thiobarbiturate zwitterions as DNA targeting agents

A series of indoleninyl-thiobarbiturate zwitterions were synthesized in up to 83 % yields from the Knoevenagel condensation between N-substituted diformyl indolenine and thiobarbiturate. The structures were characterized by spectroscopic methods such as NMR (1H, 13C), FT-IR, high-resolution mass spectrometry (HR-MS) and elemental analysis. However, their physicochemical properties and biological activities remain elusive. Herein, results from in silico ADMET calculations and cytotoxicity predictions suggest that all zwitterions are likely to exhibit a higher bioavailability and more specific cytotoxicity than doxorubicin. The notably high predicted cytotoxicity of 2d and drug-likeness score of 2f may be linked to the position of the fused benzene ring and methoxy groups, respectively. The initial biological assessment of these compounds began with in vitro DNA-binding studies because the treatment of numerous diseases such as cancer and bacterial infections is linked to DNA interactions. Zwitterion 2f demonstrated the most significant spectral change in DNA binding studies, suggesting a possible role of the methoxy group in inducing DNA binding activity. The hypothesis that 2f interacts with DNA through groove binding was confirmed by observations made during salt-back titration and DNA denaturation experiments. It was anticipated that the non-zwitterionic 2f would interact more stably with DNA (PDB code: 453D) at the minor groove than its zwitterionic form based on molecular docking calculations and molecular dynamic (MD) simulations. Additionally, the MTT assay demonstrates that 2f is moderately cytotoxic to the human breast cancer cell line MDA-MD-231, most probably as a result of the previously stated DNA binding mechanisms. Overall, the computational and in vitro data suggest the potential application of 2f as a cytotoxic DNA-targeting agent.

Tyramine Derivatives as Versatile Pharmacophores With Potent Biological Properties: Sex Hormone-Binding Globulin Inhibition, Colon Cancer Antimigration, and Antimicrobial Activity.

Guided by the idea that the presence of a heterocyclic aromatic core and tyramine moiety, under the umbrella of a single molecular scaffold could bring interesting biological properties, herein we present synthesis, characterization, with two crystal structures reported, and biological evaluation of some tyramine derivates. Cytotoxic and antimigratory potential was addressed by using a colorectal cancer cell line as a model system. Although possessing no cytotoxic effects, two compounds have shown strong antimigratory potential in low doses, with no effect on healthy MRC-5 cells. Evaluation of their antimicrobial activities suggested prominent antimicrobial activity, where Compound 4 outperformed streptomycin against Escherichia coli and Proteus mirabilis. Hormone-dependent types of cancer, such as prostate, ovary, and breast, are highly dependent on human sex hormone-binding globulin (SHBG) blood levels. A molecular docking study has shown that 1 has high affinity to bind and therefore compete with natural steroids for the SHBG steroid-binding site. DNA-binding study have shown that 4 interacts with CT-DNA in a groove-binding mode. In silico ADME/T study revealed that all compounds have suitable physicochemical properties for oral bioavailability and druglikeness, while toxicity tests for 1, 4, and 6 suggested potential for mutagenicity (4, 6), hepatotoxicity (6), and skin sensation (1).

Synthesis, Spectral Characterization and Biological, DNA Binding, Molecular Docking and ADMET Studies of a New Benzyl (Z)-N’-((E)- 3-Ethoxy-2-Hydroxybenzylidene) Carbamohydrazonothioate and Its Co (II), Ni (II), Cu (II) and Zn (II) Metal Complexes Derived From S-Benzyl Thiosemicabazide-Salicylaldehyde.

This study presents the synthesis, characterization, and biological evaluation of metal complexes derived from benzyl carbamohydrazonothioate. The ligand was synthesized through a condensation reaction and subsequently complexed with various metal ions, including Cu(II), Ni(II), Co(II), and Zn(II). The resulting metal complexes were characterized using a range of spectroscopic techniques, including FT-IR, UV-Vis, and NMR spectroscopy, confirming the successful coordination of the metal ions with the ligand. The structural elucidation was further supported by elemental analysis and molar conductance measurements. The biological activities of the synthesized complexes were evaluated for their antibacterial, antifungal, and antioxidant properties. The results indicated that the metal complexes exhibited enhanced biological activities compared to the free ligand, suggesting their potential as effective antimicrobial and antioxidant agents. This study highlights the significance of metal complexation in enhancing the biological efficacy of organic ligands.

Structural and biological studies on beta – alanine substituted Sulfonamide derivatives: A new class of Juvenile hormone mimics as insect growth regulators

A series of naphthyl-sulfonamide juvenile hormone analogs has been synthesized through one-pot synthesis route using thionyl chloride as an activating agent for carboxylic functional group. The structures of synthesized compounds with general formula C10H7-SO2NH-(CH2)2CON-R1R2 have been confirmed by FT-IR, 1HNMR , 13CNMR , and ESI-MS techniques. The insect growth regulating property of all the synthesized compounds as juvenile hormone analogs (JHAs) has been studied against yellow fever mosquito, Aedes aegypti and tobacco cutworm, Spodoptera litura. The bioassay results demonstrate that the synthesized compounds exhibit insect growth regulating activity in comparison to standard JHAs. The IE50 and IE90 values of B4 are 0.08 and 6.62 ppm, respectively for inhibition of Aedes aegypti and the LC50 and LC90 values of B3 are 11.03 and 45.36 ppm, respectively for Spodoptera litura. Notably, the compounds B3 and B4 showed enhanced efficacy at lower concentrations. Additionally, density functional theory (DFT) technique is used to predict the chemical reactivity and toxicity of the synthesized JHAs in comparison to pyriproxyfen. Further, the DNA-binding study of synthesized JHAs has been carried out using UV–vis spectroscopy for toxicity assessment against DNA and the binding constant values in the range 102 – 103 suggest lower toxicity of all the synthesized molecules in comparison to PYR. All the synthesized JHAs show IGR action and exhibit better reactivity and reduced toxicity as compared to the commercial in use IGRs.

Titania Doped CDs as Effective CT‐DNA Binders: A Novel Fluorescent Probe via Green Synthesis

AbstractCarbon dots (CDs), which belong to the class of zero‐dimensional carbon‐based nanomaterials, have garnered significant interest owing to their wide array of applications spanning from the electronics industry to the healthcare sector. This work employs a facile, inexpensive approach to synthesize green luminescent carbon dots (J‐10) from a potential medicinal plant named Justicia Wynaadensis by the one‐step hydrothermal method. A nanocomposite (JT‐10) of the CDs is prepared by adding TiO2 nanoparticles derived from green synthesis of Lavandula leaves. The J‐10 and JT‐10 are further characterized by X‐ray Diffraction spectroscopy (XRD), Transmission Electron Microscopy (TEM), Raman analysis X‐ray Photoelectron Spectroscopy (XPS), and Fourier transform infrared techniques (FTIR), UV–vis spectroscopy, Photoluminescence (PL), and Fluorescence or PL lifetime analysis. The average size of synthesized CDs is 1.85 nm and exhibits an excitation‐dependent fluorescence nature at 320 nm. PL lifetime analysis of J‐10 and JT‐10 is calculated to be 5.80 and 2.84 ns respectively. Offering these unique optical properties and biocompatibility, the synthesised material is suitable for investigating their binding affinity and interaction mechanisms with DNA. The use of JT‐10 in DNA binding studies contributes to the development of sustainable and efficient nanomaterials for applications in biosensors, drug delivery, and gene therapy.

Exploration of 4-tolyl-5-(p-tolyloxymethyl)-4H-1,2,4-triazole thioethers as potent 15-LOX inhibitors supported by in vitro, in silico, MD simulation and DNA binding studies

Inflammation is an intricate process exacerbated by the sequential release of lipid mediators during arachidonic acid metabolism through the LOX and COX pathways. The inhibition of enzymes accountable for the arachidonic acid metabolism is attributed to a synergistic anti-inflammatory impact with a broader spectrum of activity. The present study was concerned with the search for lead 15-LOX inhibitors. A new series of alkyl/aralkyl substituted 4-tolyl-5-(p-tolyloxymethyl)-4H-1,2,4-triazole (6a-h) was designed, synthesized, and characterized to determine their 15-LOX inhibitory potential. The analogue 3-(phenethylthio)-4-tolyl-5-(p-tolyloxymethyl)-4H-1,2,4-triazole (6h) was the most potent with IC50 2.73 ± 0.15 µM while 6g, 6d, 6f, 6c exhibited excellent inhibitory activities with IC50 values between 11.39 ± 0.13 and 14.63 ± 0.17 µM. All analogues maintained > 72 % blood mononuclear cells viability at 0.25 mM concentration during MTT assay. In silico ADME profiles predicted druggability potential. The molecular docking studies disclosed binding free energies of -9.78 to -7.94 kcal/mol and His373 and His378 were majorly involved in π-interactions in all molecules. Van der Waals interactions dominated hydrogen bonding in the stabilization of ligand-receptor complexes. MD simulations and free energy calculations revealed the significance of complexes in stabilizing the biomolecular system and helped in identifying the key active site residues that contributed towards the energetics. Studies against DNA dodecamer displayed minor groove binding and intercalation, suggesting a possible role in modulating DNA-related processes. The results approve the active analogues possessing promising druglike properties and work is in progress on the synthesis of more analogues in search for leads as 15-LOX inhibitors.

DNA Interaction, Molecular Docking, Antimicrobial, Anticancer and Thermal Studies of Ternary Metal Complexes of N‐Methylbenzylamine and Ethylenediamine

ABSTRACTN‐Methylbenzylamine and ethylenediamine were utilized as primary and auxiliary ligands, respectively, alongside metal salts to synthesize ternary metal complexes: [FeCl3(Nmba)(en)], [CoCl2(Nmba)(en)(H2O)] and [CuCl2(Nmba)(en)(H2O)]. These complexes were thoroughly characterized using spectral and analytical techniques, revealing an octahedral geometry for all. Coats–Redfern calculations indicated their non‐spontaneous nature yet highlighted their thermal stability. DNA binding studies unveiled a groove binding mode for the complexes, with intrinsic binding constants (Kb) and Stern–Volmer quenching constant (Ksq) supporting their strong binding capabilities. Nuclease activity against pBR322 was assessed through gel electrophoresis. Additionally, docking studies using AutoDock 4.2 software provided insights into their binding affinities. In terms of biological activities, the Cu complex demonstrated superior cytotoxicity and antibacterial and antifungal properties compared to the other ternary metal complexes. This suggests its potential for further exploration in biomedical applications.

DNA binding studies and in-vitro anticancer studies of novel lanthanide complexes

Pancreatic cancer, is an aggressive type of cancer and the most common malignancy with a poor prognosis regarding metastatic disease (survival < 10 %). The development of Novel chemotherapeutic drugs holds significant prospects for practical applications. Here, this work focuses on the interaction between two lanthanide complexes, Yb-BZA and Er-BZA, with DNA, as well as their anticancer activity against pancreatic cancer. The relationship between complexes and DNA is revealed by fluorescence, absorption spectral titration, cyclic voltammetric (CV) experiments, indicating that the Yb-BZA and Er-BZA interact with FS-DNA by bind groove. Moreover, molecular docking technology was utilized to confirm the binding of Yb-BZA and Er-BZA with 1BNA and 4AV1. The cytotoxic effects of Yb-BZA and Er-BZA on cancer cells BxPC-3 were evaluated, Yb-BZA (IC50 = 6.459 μg/mL) is more effective than oxaliplatin (IC50 = 16.46 μg/mL) evaluated using cytotoxicity assay. Yb-BZA and Er-BZA has the potential to become a chemotherapy drug for pancreatic cancer cells.

Design and synthesis of two new thiosemicarbazide based Schiff base metal complexes of nickel (II): DNA binding study and cytotoxicity profile analysis

Two new nickel (II) substituted thiosemicarbazone Schiff base complexes [Ni(meph)2] (1) [where H2meph = (2E)-N-methyl-2-[1-(pyridin-2-yl)ethylidene]hydrazine-1-carbothioamide] and [Ni(hmm)2](NO3)2·2H2O (2) [where H2hmm = (2E)-2-[(2-hydroxyphenyl)methylidene]-N-methylhydrazine-1-carbothioamide] have been designed and synthesized by the condensation of 4-methyl-3-thiosemicarbazide with 2-acetylpyridine and salicylaldehyde respectively. Both the metal complexes 1 and 2 are characterized using different available spectroscopic techniques like FT-IR, UV–Vis spectroscopy, elemental analysis, and single crystal X-ray structure analysis. X-ray crystal structure analysis reveal that complex 1 and 2 are octahedral Ni(II) complexes. The calf-thymus CT-DNA-binding property of 1 and 2 has been evaluated by employing UV–Vis and fluorescence spectral titration. All the results show that CT-DNA binds with both nickel(II) complexes 1 and 2. In vitro cytotoxicity activity of complexes 1 and 2 toward A375 and MDA-MB-231 was evaluated using MTT assay and other methods which confirm that both complexes 1 and 2 behave as promising anti-cancer agents.

Inclusion complexes of novel formyl chromone Schiff bases with β-Cyclodextrin: Synthesis, characterization, DNA binding studies and in-vitro release study

The present study involved the synthesis of five novel Schiff bases (SB1-SB5) of formyl chromone and their inclusion complexes with β-cyclodextrin through kneading approach to enhance the solubility and stability of SBs. Characterization was conducted using FTIR, NMR, SEM, TEM, p-XRD, and Mass Spectrometry. UV fluorescence and pH stability studies confirmed the formation of the inclusion complex. Structural validation of complexes was conducted via molecular docking (PDB ID: 1BFN) and 50 ns MD simulation study. DFT studies were performed on SBs using B3LYP/6–31 + G(d,p) basis set. All SBs exhibited favorable ADME properties and high binding interactions were observed in molecular docking with ctDNA (PDB Id: 1BNA). Further, in-vitro UV absorption and fluorescence experiments demonstrated strong ctDNA interactions for all Schiff bases, with binding constants in the order of 105 M−1, indicating groove binding mode. Among the SBs, SB4 exhibited the highest affinity for DNA grooves, with a binding constant (Kb) of 1.7 × 106 M−1. However, the SB4/β-Cyd inclusion complex also interacted with DNA but with low binding constants compared to SB4. An in-vitro release study of SB4/β-Cyd, revealed 78.92 % dissolution of the inclusion complex, highlighting its potential for enhanced solubility and stability in biological systems.

Synthesis, spectral elucidation and DNA binding studies of cadmium(II) carboxylates with nitrogen donor heteroligands

A new series of novel homoleptic and heteroleptic Cd(II) complexes using cyclopropanecarboxylic acid (HL1) and cyclopentanecarboxylic acid (HL2) as main ligands and N-donor species like 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen), and 2,9-dimethyl-1,10-phenanthroline (Me2phen) as co-ligands were prepared and characterized by FT-IR, multinuclear (1H and 13C) NMR, and UV–Visible spectroscopies. Furthermore, the crystal structure of the Cd(II) complex coordinated by cyclopentanecarboxylic acid (HL2) and 1,10-phenanthroline (phen) was explored by single crystal X-ray diffraction (SC-XRD) analysis. The crystal structure was binuclear, in which the coordination geometry around each cadmium center was distorted pentagonal bipyramidal coordination geometry. Various intermolecular interactions were accountable for stabilizing the supramolecular associations, which were seen by Hirshfeld surface analysis in terms of interatomic contacts. The spectroanalytical data of the synthesized complexes confirm the absence of the –OH band in the spectra of complexes as compared to the spectra of the free ligands, which favour the formation of complexes. The nature of complex-DNA interaction and the effect of the coordination of heteroligands on the binding strength of complexes were probed through UV–Visible spectroscopy and cyclic voltammetry. The obtained data confirm that the interaction of DNA with the complexes is dual: intercalation as well as groove binding. The DNA binding constants (Kb) and Gibb’s free energy changes (ΔG) were also determined for these complexes. This study aims to project effective drugs with the least harmful effects that could be useful for mankind against dreadful diseases.