Search Results (33)

This study aimed to design dual-responsive chitosan–polylactic acid nanosystems (PLA@CS NPs) for controlled and targeted ledipasvir (LED) delivery to HepG2 liver cancer cells, thereby reducing the systemic toxicity and improving the therapeutic selectivity. Two formulations were developed utilizing ionotropic gelation and w/o/w emulsion techniques: LED@CS NPs with a size of 143 nm, a zeta potential of +43.5 mV, and a loading capacity of 44.1%, and LED-PLA@CS NPs measuring 394 nm, with a zeta potential of +33.3 mV and a loading capacity of 89.3%, with the latter demonstrating significant drug payload capacity. Since most drugs work through interaction with DNA, the in vitro affinity of DNA to LED and its encapsulated forms was assessed using stopped-flow and other approaches. They bind through multi-modal electrostatic and intercalative modes via two reversible processes: a fast complexation followed by a slow isomerization. The overall binding activation parameters for LED (cordination affinity, K_a = 128.4 M⁻¹, K_d = 7.8 × 10⁻³ M, ΔG = −12.02 kJ mol⁻¹), LED@CS NPs (K_a = 2131 M⁻¹, K_d = 0.47 × 10⁻³ M, ΔG = −18.98 kJ mol⁻¹) and LED-PLA@CS NPs (K_a = 22026 M⁻¹, K_d = 0.045 × 10⁻³ M, ΔG = −24.79 kJ mol⁻¹) were obtained with a reactivity ratio of 1/16/170 (LED/LED@CS NPs/LED-PLA@CS NPs). This indicates that encapsulation enhanced the interaction between the DNA and the LED-loaded nanoparticle systems, without changing the mechanism, and formed thermodynamically stable complexes. The drug release kinetics were assessed under tumor-mimetic conditions (pH 5.5, 10 mM GSH) and physiological settings (pH 7.4, 2 μM GSH). The LED@CS NPs and LED-PLA@CS NPs exhibited drug release rates of 88.0% and 73%, respectively, under dual stimuli over 50 h, exceeding the release rates observed under physiological conditions, which were 58% and 54%, thereby indicating that the LED@CS NPs and LED-PLA@CS NPs systems specifically target malignant tissue. Release regulated by Fickian diffusion facilitates tumor-specific payload delivery. Although encapsulation did not enhance the immediate cytotoxicity compared to free LED, as demonstrated by an in vitro cytotoxicity in HepG2 cancer cell lines, it significantly enhanced the therapeutic index (2.1-fold for LED-PLA@CS NPs) by protecting non-cancerous cells. Additionally, the nanoparticles demonstrated broad-spectrum antibacterial effects, suggesting efficacy in the prevention of chemotherapy-related infections. The dual-responsive LED-PLA@CS NPs allowed controlled tumor-targeted LED delivery with better selectivity and lower off-target toxicity, making LED-PLA@CS NPs interesting candidates for repurposing HCV treatments into safer cancer nanomedicines. Furthermore, this thorough analysis offers useful reference information for comprehending the interaction between drugs and DNA. Full article

One of the most interesting and poorly studied carriers of medicinal substances is the polymer clay composite material (PCCM). Bentonite clays are used in pharmacy for the manufacturing of various dosage forms, as well as in the adsorption of drugs to slow their release. Polymer–clay nanocomposites have demonstrated significantly improved properties compared to pure polymers. A review of recent scientific advances has shown promising results regarding the application of polymer–clay materials in medicine and bioengineering, particularly in the development of carrier sorbents with prolonged action for controlled drug release. As a result, interest in polymer–clay systems is steadily growing and gaining momentum. This paper focuses on the structure and properties of bentonite clays, including their sorption, ion exchange, binding, and rheological properties. The methods for preparing intercalated and exfoliated nanocomposites, such as radical intercalative polymerization in situ on clay surfaces, are reviewed. Furthermore, the improved efficacy and exposure times of PCCMs, combined with their enhanced bactericidal properties, are analyzed for the creation of universal and multifunctional preparations for medical use. Full article

Nine manganese(II) complexes with a series of non-steroidal anti-inflammatory drugs (namely sodium diclofenac, diflunisal, flufenamic acid, sodium meclofenamate, mefenamic acid, and tolfenamic acid) were prepared in the presence of diverse nitrogen donors, i.e., pyridine, 1,10–phenanthroline, 2,2′–bipyridine and neocuproine, as co-ligands and were characterized with spectroscopic techniques and single-crystal X-ray crystallography. The biological profile of the resultant complexes was investigated regarding their antioxidant potency and their interaction with DNA and serum albumins. The complexes interact with calf–thymus DNA in an intercalative mode and bind tightly and reversibly to human and bovine serum albumins studied. In order to assess the antioxidant activity of the Mn(II) complexes, their ability to scavenge 2,2′–azinobis(3–ethylbenzothiazoline–6–sulfonic acid) free radicals was monitored. Full article

The proton transfer (PT) complexation reaction between 3,4-diaminopyridine (3,4-DAP), an important drug, and 2,6-dichloro-4-nitrphenole (DCNP) was investigated experimentally and theoretically. The experimental results indicated a chemical reaction occurred because of a hydrogen bonding, followed by proton transfer from the DCNP to the 3,4-DAP in different polar media. The Benesi–Hildebrand equation was used to estimate the formation constant (K_f), molar absorptivity (ε_PT), and other physical parameters. The formed PT complex was characterized using FTIR, ¹H, and ¹³C NMR spectra. In addition, the nanocrystalline structure, particle sizes, and surface morphology of the complex were investigated by XRD and SEM-EDX. The structure of the 1:1 PT complex was calculated theoretically in the gas phase and the presence of solvent effects. Using TD-DFT calculations, the band observed at 406 nm (Calc. 379.5 nm) and 275 nm (Calc. 272.3 nm) could be assigned to the HOMO→LUMO transition (99%), and HOMO→L+3 transition (87%), respectively. The DNA binding ability of the PT complex was investigated, revealing an intercalative binding mechanism with a binding constant K_b of 4.6 × 10⁴ M⁻¹. Based on the results of the Ct-DNA binding study, the binding free energy of the PT complex with the receptor of human DNA (PDB ID:1BNA) is found to be −7.2 kcal/mol. The cytotoxic effects of the PT complex were evaluated on selected cancer cell lines, demonstrating significant antitumor activity against A-549 and MCF-7 cancer cell lines. Full article

This study explores the interaction between Vemurafenib (VEM), a potent BRAF inhibitor, and calf thymus DNA (ctDNA) using a comprehensive array of biophysical and computational techniques. The primary objective is to understand the potential off-target effects of VEM on DNA, given its established role in melanoma therapy targeting the BRAF V600E mutation. The investigation employed methods such as ultraviolet–visible absorption spectroscopy, steady-state fluorescence, circular dichroism, isothermal titration calorimetry, and advanced molecular dynamics simulations. The results indicate that VEM interacts with DNA primarily through a minor groove-binding mechanism, causing minimal structural disruption to the DNA double helix. Viscosity measurements and melting temperature analyses further confirmed this non-intercalative mode of binding. Calorimetry data revealed an exothermic, thermodynamically favorable interaction between VEM and ctDNA, driven by both enthalpic and entropic factors. Finally, computer simulations identified the most probable binding site and mode of VEM within the minor groove of the nucleic acid, providing a molecular basis for the experimental findings. Full article

To better understand the mechanism of action of the compounds in the ethanolic extracts of J. nigra leaves and green husks, their binding to CT-DNA was investigated. This study was conducted to elucidate the in vitro protective effect of extracts against chromosomal damage in mitogen-induced human lymphocytes and investigate the possible application of selec+ted extracts as a natural source of polyphenolic compounds. Using HPLC-MS analysis, 103 different compounds were identified as having a higher number of active species, which is consistent with their activity. The frequency of micronuclei (MN) was scored in binucleated cells, and the nuclear proliferation index was calculated. Cyclic voltammetry experiments demonstrate that the nature of the interaction between extracts and CT-DNA is a synergy of electrostatic and intercalative modes, where leaves extracts showed a higher ability to bind to DNA. Extracts showed excellent antioxidant activity. At a concentration of only 4 µg/mL, extract of J. nigra leaves and the green husks reduced the incidence of MN by 58.2% and 64.5%, respectively, compared to control cell cultures. Full article

The interactions with calf thymus DNA (CT-DNA) of three Schiff bases formed by the condensation of hesperetin with benzohydrazide (HHSB or L¹H₃), isoniazid (HIN or L²H₃), or thiosemicarbazide (HTSC or L³H₃) and their Cu^II complexes (CuHHSB, CuHIN, and CuHTSC with the general formula [CuLⁿH₂(AcO)]) were evaluated in aqueous solution both experimentally and theoretically. UV–Vis studies indicate that the ligands and complexes exhibit hypochromism, which suggests helical ordering in the DNA helix. The intrinsic binding constants (K_b) of the Cu compounds with CT-DNA, in the range (2.3–9.2) × 10⁶, from CuHTSC to CuHHSB, were higher than other copper-based potential drugs, suggesting that π–π stacking interaction due to the presence of the aromatic rings favors the binding. Thiazole orange (TO) assays confirmed that ligands and Cu complexes displace TO from the DNA binding site, quenching the fluorescence emission. DFT calculations allow for an assessment of the equilibrium between [Cu(LⁿH₂)(AcO)] and [Cu(LⁿH₂)(H₂O)]⁺, the tautomer that binds Cu^II, amido (am) and not imido (im), and the coordination mode of HTSC (O⁻, N, S), instead of (O⁻, N, NH₂). The docking studies indicate that the intercalative is preferred over the minor groove binding to CT-DNA with the order [Cu(L¹H₂^am)(AcO)] > [Cu(L²H₂^am)(AcO)] ≈ TO ≈ L¹H₃ > [Cu(L³H₂^am)(AcO)], in line with the experimental K_b constants, obtained from the UV–Vis spectroscopy. Moreover, dockings predict that the binding strength of [Cu(L¹H₂^am)(AcO)] is larger than [Cu(L¹H₂^am)(H₂O)]⁺. Overall, the results suggest that when different enantiomers, tautomers, and donor sets are possible for a metal complex, a computational approach should be recommended to predict the type and strength of binding to DNA and, in general, to macromolecules. Full article

Three neutral nickel(II) complexes of 3,5–dibromo–salicylaldehyde (3,5–diBr–saloH) were synthesized in the presence or absence of 1,10–phenanthroline (phen) or its derivative 2,9–dimethyl–1,10–phenanthroline (neoc) as co–ligands, namely [Ni(3,5–diBr–salo)₂(neoc)] (complex 1), [Ni(3,5–diBr–salo)₂(phen)] (complex 2) and [Ni(3,5–diBr–salo)₂(H₂O)₂] (complex 3), and were characterized by various techniques. The crystal structure of [Ni(3,5–diBr–salo)₂(neoc)] was determined by single-crystal X-ray crystallography. According to employed studying techniques, the complexes interact tightly with calf-thymus DNA by an intercalative fashion. Furthermore, compounds 1–3 bind tightly and reversibly to human and bovine serum albumin. Full article

Precise DNA quantification and nuclear imaging are pivotal for clinical testing, pathological diagnosis, and drug development. The detection and localization of mitochondrial DNA serve as crucial indicators of cellular health. We introduce a novel conjugated oligoelectrolyte (COE) molecule, COE-S3, featuring a planar backbone composed of three benzene rings and terminal side chains. This unique amphiphilic structure endows COE-S3 with exceptional water solubility, a high quantum yield of 0.79, and a significant fluorescence Stokes shift (λ_ex = 366 nm, λ_em = 476 nm), alongside a specific fluorescence response to DNA. The fluorescence intensity correlates proportionally with DNA concentration. COE-S3 interacts with double-stranded DNA (dsDNA) through an intercalation binding mode, exhibiting a binding constant (K) of 1.32 × 10⁶ M⁻¹. Its amphiphilic nature and strong DNA affinity facilitate its localization within mitochondria in living cells and nuclei in apoptotic cells. Remarkably, within 30 min of COE-S3 staining, cell vitality can be discerned through real-time nuclear fluorescence imaging of apoptotic cells. COE-S3’s high DNA selectivity enables quantitative intracellular DNA analysis, providing insights into cell proliferation, differentiation, and growth. Our findings underscore COE-S3, with its strategically designed, shortened planar backbone, as a promising intercalative probe for DNA quantification and nuclear imaging. Full article

The interactions of dsDNA with new targeted drug delivery derivatives of doxorubicin (DOX), such as DOX embedded into phospholipid nanoparticles (NPhs) and DOX with the NGR targeted peptide-modified NPhs were studied electrochemically by differential pulse voltammetry technique. Screen-printed electrodes (SPEs), modified with stable fine dispersions of carbon nanotubes (CNTs), were used for quantitative electrochemical investigations of direct electrochemical oxidation of guanine, adenine, and thymine heterocyclic bases of dsDNA, and their changes in the presence of DOX nanoderivatives. Analysing the shifts of peak potentials of nucleobases in the presence of drug, we have shown that the doxorubicin with NGR targeted peptide changed the mode of interaction in DNA–drug complexes from intercalative to electrostatic. Binding constants (K_b) of DNA–drug complexes were calculated in accordance with adenine, guanine, and thymine oxidation signals. Based on our experiments, we have proven that the surface modification of a drug delivery system with NGR targeted peptide dramatically changed the mechanism of interaction of drug with genetic material. DNA-mediated drug toxicity was calculated based on the concentration-dependent “response” of heterocyclic nucleobases on drug influence. DOX, DOX-loaded phospholipid nanoparticles (NPhs), and DOX with NGR addressed peptide-modified NPhs were moderately toxic in the concentration range of 0.5–290 µM. Full article

A new chlorobenzylidene imine ligand, (E)-1-((5-chloro-2-hydroxybenzylidene)amino) naphthalen-2-ol (HL), and its [Zn(L)(NO₃)(H₂O)₃], [La(L)(NO₃)₂(H₂O)₂], [VO(L)(OC₂H₅)(H₂O)₂], [Cu(L)(NO₃)(H₂O)₃], and [Cr(L)(NO₃)₂(H₂O)₂], complexes were synthesized and characterized. The characterization involved elemental analysis, FT-IR, UV/Vis, NMR, mass spectra, molar conductance, and magnetic susceptibility measurements. The obtained data confirmed the octahedral geometrical structures of all metal complexes, while the [VO(L)(OC₂H₅)(H₂O)₂] complex exhibited a distorted square pyramidal structure. The complexes were found to be thermally stable based on their kinetic parameters determined using the Coats–Redfern method. The DFT/B3LYP technique was employed to calculate the optimized structures, energy gaps, and other important theoretical descriptors of the complexes. In vitro antibacterial assays were conducted to evaluate the complexes’ potential against pathogenic bacteria and fungi, comparing them to the free ligand. The compounds exhibited excellent fungicidal activity against Candida albicans ATCC: 10231 (C. albicans) and Aspergillus negar ATCC: 16404 (A. negar), with inhibition zones of HL, [Zn(L)(NO₃)(H₂O)₃], and [La(L)(NO₃)₂(H₂O)₂] three times higher than that of the Nystatin antibiotic. The DNA binding affinity of the metal complexes and their ligand was investigated using UV-visible, viscosity, and gel electrophoresis methods, suggesting an intercalative binding mode. The absorption studies yielded K_b values ranging from 4.40 × 10⁵ to 7.30 × 10⁵ M⁻¹, indicating high binding strength to DNA comparable to ethidium bromide (value 10⁷ M⁻¹). Additionally, the antioxidant activity of all complexes was measured and compared to vitamin C. The anti-inflammatory efficacy of the ligand and its metal complexes was evaluated, revealing that [Cu(L)(NO₃)(H₂O)₃] exhibited the most effective activity compared to ibuprofen. Molecular docking studies were conducted to explore the binding nature and affinity of the synthesized compounds with the receptor of Candida albicans oxidoreductase/oxidoreductase INHIBITOR (PDB ID: 5V5Z). Overall, the combined findings of this work demonstrate the potential of these new compounds as efficient fungicidal and anti-inflammatory agents. Furthermore, the photocatalytic effect of the Cu(II) Schiff base complex/GO was examined. Full article

Diaryl-furanones are specific analytical reagents for the biochemical detection of primary amines by fluorescence techniques. Well-known reagents are fluorescamine (Fluram) and 2-methoxy-2,4-diphenyl-3(2H)-furanone (MDPF), yielding fluorescent products with λem at 480–490 nm. Although the reaction products claim to be pyrrolinones, recent studies show that they are really 3-oxopyrrole (pyrrolone) derivatives. Both reagents have been used for the cytochemical demonstration of primary amines. In this work, we have applied the fluorescent products of MDPF with amines (n-butylamine, BA; glucosamine, GA; and spermine, Sp), which showed interesting fluorescence reactions with chromatin DNA. 2,4-diphenyl-3-oxopyrrole products (diPOPy) can be easily synthesized according to well-known procedures, by mixing solutions of MDPF in acetone with water at pH 9 containing the amino compounds. DiPOPy derivatives of BA, GA, and Sp were used for spectroscopic, microscopic, and molecular modeling studies, showing a bright and selective blue–green fluorescence on DNA substrates, mainly chromatin, kinetoplast DNA, and stretched chromatin fibers. The cationic diPOPy fluorophore is planar, with a high partial positive charge in the N atom, and suitable for intercalative binding to DNA. A mechanism of fluorescamine fluorescence due to an inner-salt isomeric form is proposed, and an astonishing correlation between adenine–thymine-rich centromeric heterochromatin in mouse metaphase chromosomes after reaction of the fluorescamine reagent with protein amino groups is also discussed. Full article

Six heteroleptic Cu(II) carboxylates (1–6) were prepared by reacting 2-chlorophenyl acetic acid (L¹), 3-chlorophenyl acetic acid (L²), and substituted pyridine (2-cyanopyridine and 2-chlorocyanopyridine). The solid-state behavior of the complexes was described via vibrational spectroscopy (FT-IR), which revealed that the carboxylate moieties adopted different coordination modes around the Cu(II) center. A paddlewheel dinuclear structure with distorted square pyramidal geometry was elucidated from the crystal data for complexes 2 and 5 with substituted pyridine moieties at the axial positions. The presence of irreversible metal-centered oxidation reduction peaks confirms the electroactive nature of the complexes. A relatively higher binding affinity was observed for the interaction of SS-DNA with complexes 2–6 compared to L¹ and L². The findings of the DNA interaction study indicate an intercalative mode of interaction. The maximum inhibition against acetylcholinesterase enzyme was caused for complex 2 (IC₅₀ = 2 µg/mL) compared to the standard drug Glutamine (IC₅₀ = 2.10 µg/mL) while the maximum inhibition was found for butyrylcholinesterase enzyme by complex 4 (IC₅₀ = 3 µg/mL) compared to the standard drug Glutamine (IC₅₀ = 3.40 µg/mL). The findings of the enzymatic activity suggest that the under study compounds have potential for curing of Alzheimer’s disease. Similarly, complexes 2 and 4 possess the maximum inhibition as revealed from the free radical scavenging activity performed against DPPH and H₂O₂. Full article

This work aimed to evaluate in vitro DNA binding mechanistically of cationic nitrosyl ruthenium complex [RuNOTSP]⁺ and its ligand (TSPH₂) in detail, correlate the findings with cleavage activity, and draw conclusions about the impact of the metal center. Theoretical studies were performed for [RuNOTSP]⁺, TSPH₂, and its anion TSP⁻² using DFT/B3LYP theory to calculate optimized energy, binding energy, and chemical reactivity. Since nearly all medications function by attaching to a particular protein or DNA, the in vitro calf thymus DNA (ctDNA) binding studies of [RuNOTSP]⁺ and TSPH₂ with ctDNA were examined mechanistically using a variety of biophysical techniques. Fluorescence experiments showed that both compounds effectively bind to ctDNA through intercalative/electrostatic interactions via the DNA helix’s phosphate backbone. The intrinsic binding constants (K_b), (2.4 ± 0.2) × 10⁵ M⁻¹ ([RuNOTSP]⁺) and (1.9 ± 0.3) × 10⁵ M⁻¹ (TSPH₂), as well as the enhancement dynamic constants (K_D), (3.3 ± 0.3) × 10⁴ M⁻¹ ([RuNOTSP]⁺) and (2.6 ± 0.2) × 10⁴ M⁻¹ (TSPH₂), reveal that [RuNOTSP]⁺ has a greater binding propensity for DNA compared to TSPH₂. Stopped-flow investigations showed that both [RuNOTSP]⁺ and TSPH₂ bind through two reversible steps: a fast second-order binding, followed by a slow first-order isomerization reaction via a static quenching mechanism. For the first and second steps of [RuNOTSP]⁺ and TSPH₂, the detailed binding parameters were established. The total binding constants for [RuNOTSP]⁺ (K_a = 43.7 M⁻¹, K_d = 2.3 × 10⁻² M⁻¹, ΔG⁰ = −36.6 kJ mol⁻¹) and TSPH₂ (K_a = 15.1 M⁻¹, K_d = 66 × 10⁻² M, ΔG⁰ = −19 kJ mol⁻¹) revealed that the relative reactivity is approximately ([RuNOTSP]⁺)/(TSPH₂) = 3/1. The significantly negative ΔG⁰ values are consistent with a spontaneous binding reaction to both [RuNOTSP]⁺ and TSPH₂, with the former being very favorable. The findings showed that the Ru(II) center had an effect on the reaction rate but not on the mechanism and that the cationic [RuNOTSP]⁺ was a more highly effective DNA binder than the ligand TSPH₂ via strong electrostatic interaction with the phosphate end of DNA. Because of its higher DNA binding affinity, cationic [RuNOTSP]⁺ demonstrated higher cleavage efficiency towards the minor groove of pBR322 DNA via the hydrolytic pathway than TSPH₂, revealing the synergy effect of TSPH₂ in the form of the complex. Furthermore, the mode of interaction of both compounds with ctDNA has also been supported by molecular docking. Full article

Ochratoxin A (OTA) is positively correlated with an increased risk of developing cancer in nephrotoxic and hepatotoxic patients. Therefore, it is of great significance for the highly sensitive, highly selective, and timely detection of OTA. We described here an electrochemical aptasensor for OTA analysis, which took advantage of the favorable properties of gold nanoparticles (AuNPs) functionalized zinc oxide (ZnO) composites and the intercalative binding between methylene blue (MB) and nucleic acid. There were two label-free aptamers: one to capture OTA and another serving as complementary DNA (cDNA), enabling connection to the ZnO-Au composite’s immobilized electrode. Once OTA was present, the aptamer could capture OTA and detach from the electrode interface, thus, preventing MB from accessing electrode surface for efficient electron transfer; a decreased peak current was monitored by differential pulse voltammetry. The aptasensor presented nice analytical performance for OTA detection in the range of 0.1–30,000 pg·mL⁻¹, with a detection limit of 0.05 pg·mL⁻¹. Moreover, the developed biosensor could be applied to actual sample (wine and beer) analysis. Full article