Search Results (287)

A novel ruthenium(II) complex, [RuCl₂(η⁶-p-cymene)(bph-κN)] (1), was synthesized and structurally characterized using FTIR and NMR spectroscopy. Density functional theory (DFT) calculations supported the proposed geometry and allowed for comparative analysis of experimental and theoretical spectroscopic data. The interaction of complex 1 with human serum albumin (HSA) and calf thymus DNA was investigated through fluorescence quenching experiments, revealing spontaneous binding driven primarily by hydrophobic interactions. The thermodynamic parameters indicated mixed quenching mechanisms in both protein and DNA systems. Ethidium bromide displacement assays and molecular docking simulations confirmed DNA intercalation as the dominant binding mode, with a Gibbs free binding energy of −34.1 kJ mol⁻¹. Antioxidant activity, assessed by EPR spectroscopy, demonstrated effective scavenging of hydroxyl and ascorbyl radicals. In vitro cytotoxicity assays against A375, MDA-MB-231, MIA PaCa-2, and SW480 cancer cell lines revealed selective activity, with pancreatic and colorectal cells showing the highest sensitivity. QTAIM analysis provided insight into metal–ligand bonding characteristics and intramolecular stabilization. These findings highlight the potential of 1 as a promising candidate for further development as an anticancer agent, particularly against multidrug-resistant tumors. Full article

Niacinamide was recently shown to directly interact with bacterial DNA and interfere with cell replication; niacinamide mode of interaction and efficacy as a natural anti-microbial molecule were also described. The aim of this study is to elucidate the exact binding mechanism of niacinamide to microbial DNA. Intercalation is a binding mode where a small planar molecule, such as niacinamide, is inserted between base pairs, causing structural changes in the DNA. Melting curve analysis with various intercalating dyes demonstrated that niacinamide interaction with bacterial DNA reduces its melting temperature in a linear dose-dependent manner. Niacinamide’s effect on the melting temperature was found to be % GC-dependent, while purine stretches were also found to influence the binding kinetics. Finally, fluorescent intercalator displacement (FID) assays demonstrated that niacinamide strongly reduces SYBR Safe signal in a dose-dependent manner. Interestingly, competition assays with a minor groove binder also reduced Hoechst signal but in a non-linear manner, which can be attributed to strand lengthening and unwinding following niacinamide intercalation. Taken altogether; our results suggest a “disruptive intercalation” as the mode of interaction of niacinamide with bacterial DNA. Formation of locally destabilized DNA portions by niacinamide might interfere with protein–DNA interaction and potentially affect several crucial bacterial cellular processes, e.g., DNA repair and replication, subsequently leading to cell death. Full article

Cyclic voltammetry (CV) is an accessible, readily available, non-expensive technique that can be used to search for the interaction of compounds with DNA and detect the strongest DNA-binding from a set of compounds, therefore allowing for the optimization of the number of cytotoxicity assays. Focusing on this electrochemical approach, the study of twenty-seven camphorimine silver complexes of six different families was performed aiming at detecting interactions with calf thymus DNA (CT-DNA). All of the complexes display at least two cathodic waves attributed respectively to the Ag(I)→Ag(0) (higher potential) and ligand based (lower potential) reductions. In the presence of CT-DNA, a negative shift in the potential of the Ag(I)→Ag(0) reduction was observed in all cases. Additional changes in the potential of the waves, attributed to the ligand-based reduction, were also observed. The formation of a light grey product adherent to the Pt electrode in the case of {Ag(OH)} and {Ag₂(µ-O)} complexes further corroborates the interaction of the complexes with CT-DNA detected by CV. The morphologic analysis of the light grey material was made by scanning electronic microscopy (SEM). The magnitude of the shift in the potential of the Ag(I)→Ag(0) reduction in the presence of CT-DNA differs among the families of the complexes. The complexes based on {Ag(NO₃)} exhibit higher potential shifts than those based on {Ag(OH)}, while the characteristics of the ligand (^AL-Y, ^BL-Y, ^CL-Z) and the imine substituents (Y,Z) fine-tune the potential shifts. The energy values calculated by docking corroborate the tendency in the magnitude of the interaction between the complexes and CT-DNA established by the reaction coefficient ratios (Q_[Ag-DNA]/Q_[Ag]). The molecular docking study extended the information regarding the type of interaction beyond the usual intercalation, groove binding, or electrostatic modes that are typically reported, allowing a finer understanding of the non-covalent interactions involved. The rationalization of the CV and cytotoxicity data for the Ag(I) camphorimine complexes support a direct relationship between the shifts in the potential and the cytotoxic activities of the complexes, aiding the decision on whether the cytotoxicity of a complex from a family is worthy of evaluation. Full article

Their demonstrable bioactive characteristics, coupled with their wide structural diversity and coordination versatility, render Schiff bases and their coordination complexes biologically active compounds demonstrating outstanding properties. This research describes the synthesis and characterization of new Cu(II) and Ni(II) complexes with an NNO-donor hydrazone ligand (HL). The crystal structure of the HL ligand was determined through single-crystal X-ray diffraction studies. The in vitro antibacterial activities of the HL ligand and its metal(II) complexes against Gram-positive and Gram-negative bacteria demonstrated that the metal(II) complexes displayed greater antimicrobial activities compared to the free Schiff base ligand. Furthermore, the interaction of the ligand and the complexes with calf thymus DNA (CT-DNA) was explored through electronic absorption and viscosity measurements, suggesting intercalation as the most likely mode of binding. The compounds promoted oxidative DNA cleavage, as demonstrated by the strand breaks of the pmChery plasmid under oxidative stress conditions. Finally, fluorescence spectroscopy also revealed the strong binding affinity of these compounds for bovine serum albumin (BSA). Full article

The interaction of cobalt(II) with first-generation quinolones oxolinic acid (Hoxo), flumequine (Hflmq), pipemidic acid (Hppa) and cinoxacin (Hcx) in the presence of the N,N′-donor heterocyclic ligands 2,2′-bipyridine (bipy) or 1,10-phenanthroline (phen) afforded a series of novel cobalt complexes, namely [Co(bipy)₂(oxo)](PF₆)₂·H₂O (1), [Co(phen)₂(oxo)](PF₆)₂·0.5CH₃OH·0.5H₂O (2), [Co(bipy)₂(flmq)](PF₆)₂·0.5CH₃OH·0.5H₂O (3), [Co(bipy)₂(ppa)](PF₆)₂·CH₃OH·0.5H₂O (4), [Co(phen)₂(cx)](PF₆)₂·CH₃OH·0.5H₂O (5), and [Co(phen)₂(flmq)](PF₆)·0.5CH₃OH·H₂O (6). The characterization of the complexes involved physicochemical techniques, various spectroscopies and single-crystal X-ray crystallography. The affinity of complexes to calf-thymus (CT) DNA was monitored with various techniques, suggesting intercalation in-between the DNA-nucleobases as the most probable interaction mode, which may be combined with electrostatic interactions as a result of the cationic nature of the complexes. The affinity of the complexes for bovine and human serum albumin proteins was monitored, and the determined corresponding albumin-binding constants revealed a tight and reversible interaction. Full article

A nitro-derivative of fenamic acid (4′–nitro–fenamic acid) was synthesized and used as ligand for the synthesis of four Co(II) complexes in the absence or presence of the N,N′-donors 2,2′–bipyridylamine, 1,10–phenanthroline and 2,9–dimethyl–1,10–phenanthroline. The characterization of the resultant complexes was performed with diverse techniques (elemental analysis, molar conductivity measurements, IR and UV-vis spectroscopy, single-crystal X-ray crystallography). The biological evaluation of the compounds encompassed (i) antioxidant activity via hydrogen peroxide (H₂O₂) reduction and free radical scavenging; (ii) antimicrobial screening against two Gram-positive and two Gram-negative bacterial strains; (iii) interactions with calf-thymus (CT) DNA; (iv) cleavage of supercoiled pBR322 plasmid DNA (pDNA), in the dark or under UVA/UVB/visible light irradiation; and (v) binding affinity towards bovine and human serum albumins. The antioxidant activity of the compounds against 2,2′–azinobis–(3–ethylbenzothiazoline–6–sulfonic acid) radicals and H₂O₂ is significant, especially in the case of H₂O₂. The complexes exhibit adequate antimicrobial activity against the strains tested. The complexes interact with CT DNA through intercalation with binding constants reaching a magnitude of 10⁶ M⁻¹. The compounds have a significantly enhanced pDNA-cleavage ability under irradiation, showing promising potential as photodynamic therapeutic agents. All compounds can bind tightly and reversibly to both albumins tested. Full article

The coordination chemistry, structural characterization, and biomolecular interactions of europium(III) and iron(III) complexes with the pyridoxal-semicarbazone (PLSC) ligand were thoroughly examined using experimental and computational approaches. Single-crystal X-ray diffraction revealed that the europium complex exhibits a nine-coordinate geometry with one protonated and one deprotonated PLSC ligand and nitrato and aqua ligands. In contrast, the iron complex adopts a six-coordinate structure featuring a monoprotonated PLSC, two chlorido, and an aqua ligand. Hirshfeld surface analysis confirmed the significance of intermolecular contacts in stabilizing the crystal lattice. Theoretical geometry optimizations using DFT methods demonstrated excellent agreement with experimental bond lengths and angles, thereby validating the reliability of the chosen computational levels for subsequent quantum chemical analyses. Quantum Theory of Atoms in Molecules (QTAIM) analysis was employed to investigate the nature of metal–ligand interactions, with variations based on the identity of the donor atom and the ligand’s protonation state. The biological potential of the complexes was evaluated through spectrofluorimetric titration and molecular docking. Eu-PLSC displayed stronger binding to human serum albumin (HSA), while Fe-PLSC showed higher affinity for calf thymus DNA (CT-DNA), driven by intercalation. Thermodynamic data confirmed spontaneous and enthalpy-driven interactions. These findings support using PLSC-based metal complexes as promising candidates for future biomedical applications, particularly in drug delivery and DNA targeting. Full article

Doxorubicin is an anthracycline chemotherapeutic that is widely used for treating various malignancies, including breast cancer, lymphomas, and sarcomas. Despite its efficacy, its clinical utility is limited by a well-documented risk of cardiotoxicity, which may manifest acutely or chronically. Doxorubicin works by intercalating DNA and inhibiting topoisomerase II, leading to DNA damage and cell death. However, this mechanism is not selective to cancer cells and can adversely affect cardiac myocytes. The introduction of doxorubicin into oncologic practice has revolutionized cancer treatment, but its cardiotoxic effects remain a significant concern. This systematic review aims to comprehensively examine the multifaceted impact of doxorubicin on cardiac structure and function through both preclinical and clinical lenses. Full article

Metal complexes of endogenous metals, such as iron, copper, and zinc, offer a biocompatible, cost-effective, and eco-friendly alternative to heavy metals for drug design. This study presents the synthesis, structural characterization, and evaluation of the biological activity of eight novel iron(III) complexes with substituted salicylaldehydes as ligands. The characterization of the complexes involved spectroscopic and physicochemical methods. The structures of two complexes were determined using single-crystal X-ray crystallography. The biological studies of the complexes focused on the interaction of calf-thymus DNA, the (photo)cleavage of pBR322 plasmid DNA (pDNA), the affinity for bovine and human serum albumins, and the antioxidant activity. The complexes interacted with calf-thymus DNA via intercalation with high DNA-binding constants. The complexes exhibited high pDNA-cleavage ability, which is significantly enhanced upon exposure to UVA or UVB irradiation. The complexes can bind tightly and reversibly to both serum albumins, and their binding locations were identified. Finally, the complexes showed moderate ability to scavenge 1,1-diphenyl-picrylhydrazyl and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals with a high ability to reduce hydrogen peroxide. Full article

Background/Objectives: Aberrant expression of c-MYC drives aggressive cancers. A guanine-rich promoter sequence (Pu27) folds into a transcriptionally repressive G-quadruplex (G4). Epigallocatechin gallate (EGCG), the main green tea polyphenol, displays anticancer activity, but clear, easily replicated evidence for direct binding to the c-MYC G4 is lacking. We therefore obtained the first biophysical confirmation of an EGCG–c-MYC G4 interaction using routine UV–visible spectroscopy. Methods: A pre-annealed Pu27 G4 (5 µM) in potassium-rich buffer was titrated with freshly prepared EGCG (0–20 µM) at 25 °C. Full-range UV–Vis spectra (220–400 nm) were recorded after each addition, and absorbance variations at the DNA (260 nm) and ligand (275 nm) maxima were quantified across three independent replicates. Results: EGCG induced pronounced, concentration-dependent hyperchromicity at 260 nm, reaching ~8–10% above baseline at a 4:1 ligand/DNA ratio and exhibiting saturable binding behaviour. Concurrently, the 275 nm band displayed relative hypochromicity coupled with a subtle bathochromic shift. These reciprocal perturbations—absent in buffer-only controls—constitute definitive evidence of a specific EGCG•G4 complex most consistent with external π-stacking or groove engagement rather than intercalation. Conclusions: This study delivers the first rigorous, quantitative UV–Vis confirmation that a readily consumed dietary polyphenol directly targets the c-MYC promoter G4. By marrying conceptual elegance with methodological accessibility, it provides a compelling molecular rationale for EGCG’s anti-oncogenic repertoire, inaugurates an expedient platform for screening G4-reactive nutraceuticals, and paves the way for structural and cellular investigations en route to next-generation c-MYC-directed therapies. Full article

Background/Objectives: The thiazolo [5,4-d]pyrimidine scaffold is a class of drugs known for its anticancer, antitumor, anti-inflammatory, and antimicrobial properties. In this study, the electrochemical properties of novel thiazolo [5,4-d]pyrimidine derivatives and their interactions with DNA were characterized for the first time using voltammetric methods. Determining the interactions of new drug candidate molecules with DNA is crucial for drug development studies and is the main objective of this research. Methods: Both molecules were immobilized on the surface of the electrodes by passive adsorption, and their electrochemical properties were determined by voltammetric methods through reduction currents. Their interactions with DNA were carried out in the solution phase and examined by the changes in the oxidation peak potential and current of the guanine base. Results: For both molecules, it was determined that the electrochemical reduction processes are diffusion-controlled and irreversible, with an equal number of protons and electrons being transferred during this process. The detection limits for TP-NB (4-chloro-N-(5-chlorothiazolo [5,4-d]pyrimidin-2-yl)-3-nitrobenzamide) and TP-PC (1-(2-(4-(4-carbamoylpiperidin-1-yl)-3-nitrobenzamido)thiazolo [5,4-d]pyrimidin-5-yl)piperidine-4-carboxamide) were determined to be 12 µg/mL and 16 µg/mL, respectively. As a result of the interaction between both molecules with DNA, the guanine oxidation current decreased. It was found that TP-NB could act as an intercalator, while TP-PC could affect DNA electrostatically, both showing toxic effects on DNA. Conclusions: An electrochemical method was developed for the rapid, cost-effective, and sensitive detection of both molecules and their DNA interactions. Both compounds exhibited notable affinity towards DNA, as evidenced by significant changes in oxidation peak currents, shifts in peak potentials, and calculated toxicity values. These findings suggest their potential use as DNA-interacting drugs, such as anticancer and antimicrobial agents. Our study offers a quick, cost-effective, and reliable electrochemical approach for the evaluation of drug–DNA interactions. Full article

GSH biosynthesis is enhanced in cancer cells that express the variant isoform of the surface antigen CD44 (CD44v), which is overexpressed in certain types of cancer. The GSH-responsive prodrug Ns-Dox was prepared by modifying the GSH-responsive group 2-nitrobenzene sulfonyl (Ns) with the model drug doxorubicin (Dox). Its function was evaluated based on its molecular interaction with model DNA in terms of its binding constant (K_a). The association constant of Ns-Dox was lower, and its interaction with model DNA was weaker compared to that of Dox, suggesting that Ns-Dox may act as a less toxic prodrug. HCT116 cells with high CD44v expression and GSH levels and BT474 cells with low CD44v expression and GSH levels were used. The addition of Ns-Dox to HCT116 cells produced cytotoxic effects similar to those of Dox. In contrast, a significant difference in viability was observed between Ns-Dox- and Dox-treated BT474 cells at low concentrations. These findings suggest that Ns-Dox functions as a prodrug with low environmental toxicity and a lower GSH concentration in cancer cells. It is efficiently activated to Dox in cells with high GSH production, demonstrating its cell-killing effects. Full article

Background/Objectives: TDP-43 mutation-driven Amyotrophic Lateral Sclerosis (ALS) motor neuron disease is one of the most prominent forms (approximately 97%) in cases of sporadic ALS. Dysfunctional autophagy and lysosomal function are the prime mechanisms behind ALS. Mitoxantrone (Mito), a synthetic doxorubicin analog, is an inhibitor of DNA and RNA synthesis/repair via intercalating with nitrogenous bases and inhibiting topoisomerase II. The therapeutic potential of miRNAs associated with disease conditions has also been reported. This study explores the therapeutic potential of Mito along with miRNAs against mutated TDP-43 protein-induced proteinopathy in human-induced pluripotent stem cell (hiPSC)-derived human neural progenitor cells (hNPCs). Methods: HiPSCs mutated for TDP-43 were differentiated into hNPCs and used to explore the therapeutic potential of Mito at a concentration of 1 μM for 24 h (the identified non-cytotoxic dose). The therapeutic effects of Mito on miRNA expression and various cellular parameters such as mitochondrial dynamics, autophagy, and stress granules were assessed using the high-throughput Open Array technique, immunocytochemistry, flow cytometry, immunoblotting, and mitochondrial bioenergetic assay. Results: Mutated TDP-43 protein accumulation causes stress granule formation (G3BP1), mitochondrial bioenergetic dysfunction, SOD1 accumulation, hyperactivated autophagy, and ER stress in hNPCs. The mutated hNPCs also show dysregulation in six miRNAs (miR-543, miR-34a, miR-200c, miR-22, miR-29b, and miR-29c) in mutated hNPCs. A significant restoration of TDP-43 mutation-induced alterations could be witnessed upon the exposure of mutated hNPCs to Mito. Conclusions: Our study indicates that miR-543, miR-29b, miR-22, miR-200c, and miR-34a have antisense therapeutic potential alone and in combination with Mitoxantrone. Full article

Quantitative nucleic acid detection is widely used in molecular diagnostics for infectious diseases. Here, we demonstrate that the previously developed MLFIA (magnetically localized fluorescent immunoassay) has the potential to detect Polymerase Chain Reaction (PCR) and loop-mediated isothermal amplification (LAMP) products using biotinylated and fluorescent primers and streptavidin-coated magnetic nanoparticles. The functionalized nanoparticles separate amplified DNA from non-incorporated primers in situ, allowing the quantification of DNA products. We compare magnetically localized fluorescence detection to commercial technologies based on the DNA intercalation of fluorescent dyes. Our system allows the detection of PCR and LAMP products but is approximately 10 times less sensitive than standard commercial assays. Future optimizations, such as enhancing the signal-to-noise ratio and improving nanoparticle functionalization, could significantly increase sensitivity and bring it closer to current diagnostic standards. This work highlights the potential of magnetically localized fluorescence detection to detect DNA. Full article

Lumpy skin disease virus (LSDV) affects cattle and causes significant economic damage. The live vaccine derived from an attenuated strain is effective but is associated with mild disease and skin lesions in some vaccinated cattle. Moreover, recombinant LSDV strains, particularly one with wild-type field and vaccine strains, have recently emerged and spread throughout Asian countries. A cost-effective LSDV typing method is required. We developed a multi-locus real-time PCR with a high-resolution melting (HRM) assay to differentiate between the wild-type, vaccine, and dominant Asian recombinant strains. Based on a multiple alignment analysis, we selected three target genes for the HRM assay, ORF095, ORF126, and ORF145, in which there are insertions/deletions and nucleotide substitutions between wild-type and vaccine strains, and designed primer sets for the assay. Using the synthetic DNA encoding these genes for the two strains, it was shown that the PCR amplicons intercalated with a saturating fluorescent dye could clearly differentiate between wild-type and vaccine strains in the HRM analysis for all three target genes. Further, using clinical samples, our method was able to identify recombinant strains harboring the wild-type ORF095 and ORF145 and the vaccine strain ORF126 genes. Thus, our HRM assay may provide rapid LSDV typing. Full article