DNA Interaction Research Articles

Assessing the interaction effects of mitochondrial DNA polymorphisms and lifestyle on heel bone mineral density.

Bone mineral density (BMD) is a major predictor of osteoporotic fractures, and previous studies have reported the effects of mitochondrial dysfunction and lifestyle on BMD, respectively. However, their interaction effects on BMD are still unclear. Therefore, we aimed to investigate the possible interaction of mitochondrial DNA (mtDNA) and common lifestyles contributing to osteoporosis. Our analysis included 119,120 white participants (Nfemale=65,949 and Nmale=53,171) from the UK Biobank with heel BMD phenotype data. A generalized linear regression model of PLINK was performed to assess the interaction effects of mtDNA and five life environmental factors on heel BMD, including smoking, drinking, physical activity, dietary diversity score, and vitamin D. In addition, we also performed linear regression analysis for total body BMD. Finally, we assessed the potential causal relationships between mtDNA copy number (mtDNA-CN) and life environmental factors using Mendelian randomization (MR) analysis. Our study identified four mtDNA loci showing suggestive evidence of heel BMD, such as m.16356T>C (MT-DLOOP; P =1.50×10-3) in total samples. Multiple candidate mtDNA×lifetsyle interactions were also detected for heel BMD, such as MT-ND2×physical activity (P = 2.88×10-3) in total samples and MT-ND1×smoking (P = 8.54×10-4) in males. Notably, MT-CYB was a common candidate mtDNA loci for heel BMD to interact with five life environmental factors. Multivariable MR analysis indicated a causal effect of physical activity on heel BMD when mtDNA-CN was considered (P =1.13×10-3). Our study suggests the candidate interaction between mitochondria and lifestyles on heel BMD, providing novel clues for exploring the pathogenesis of osteoporosis.

Ternary Schiff base metal (II) complexes with N,N,N′,N′-Tetramethylethylenediamine: Influence of secondary chelates on antimicrobial, scavenging activity, DNA interaction and cytotoxicity

A series of complexes involving bivalent metal ions such as cobalt, nickel, copper, and zinc were synthesized using Schiff bases derived from l-tyrosine and salicylaldehyde. Utilizing both analytical and spectroscopic methods, the compounds underwent analysis. In terms of their potential biological effects, the antioxidant properties of the samples were gauged by their ability to scavenge DPPH radicals. Notably, all the compounds demonstrated enhanced activity in this aspect, with the exception of the ligand. To investigate their impact on DNA, the compounds' capability to cleave DNA was assessed via gel electrophoresis. Remarkably, the compounds effectively induced the cleavage of supercoiled plasmid DNA. Moreover, the interaction between calf thymus DNA and the metal-imine chelates were examined. The Cu(II) complex had a significant interaction, as evidenced by its binding constant of (3.46 ± 0.02 x 105 M−1).

Computational, spectroscopic, sensor and biological studies of Cu(II) complex of Fluoro substituted Schiff base

Schiff base ligand (FHPB - 2-[N-(fluorophenyl)-4‑hydroxy-4-phenyl] 3-butene), and its copper complex Cu[FHPB]2 were prepared and the structural framework of prepared compounds were characterized by analytical, spectroscopic and DFT calculation techniques. The result suggests that, prepared Cu[FPB]2 complex possesses square planar geometry. Electrochemical studies reveal that Cu[FPB]2 complex is quasi reversible in nature. Sensing ability of prepared ligand with various cations were analyzed by absorption and emission spectral techniques and infer that the ligand FHPB is highly sensitive and selective sensor for the Cu2+ ion as compared to other selected metal ions. Antimicrobial activities of FHPB and Cu[FPB]2 against selected bacterial and fungal strains were checked by Disc Diffusion method. DNA interaction of prepared compounds were analyzed by spectrophotometric and spectrofluorometric techniques. The analysis illustrates that the synthesized compounds interact with calf thymus DNA by the way of an intercalation mode. Moreover, the binding ability of FHPB and Cu[FPB]2 were demonstrated by molecular docking and it evidences the strong binding with CT-DNA double helix.

Exploring the Interplay between Mitochondrial DNA and Lifestyle Factors in the Pathogenesis of Psychiatric Disorders

The objectives of this study were to investigate the interaction of mitochondrial DNA (mtDNA) and lifestyle factors in the development of psychiatric disorders and to gain greater insight into their pathogenesis and comorbidity. We analyzed data from approximately 150,000 individuals from the UK Biobank. Mitochondrial gene-by-environment interaction studies (mtGEIS) were performed to assess the relationships between mtDNA and psychiatric disorders, such as anxiety, depression, and self-harm. These disorders were defined using diagnostic and severity indicators derived from the General Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9). Smoking and drinking behaviors were characterized based on UK Biobank criteria. For the mtGEIS, logistic and linear regression models from PLINK 2.0 were employed, accounting for covariates like age, sex, PC1-10, Townsend Deprivation Index (TDI), and educational attainment. We also conducted sex-stratified analyses to detect any gender-specific effects. Our findings highlighted significant associations between mtDNA and three psychiatric disorders. Moreover, the interplay between mtDNA and lifestyle factors showed significant associations with psychiatric disorders (all P values < 0.05). Specifically, two mutant loci, T5004C (BAnx_self=−0.0026, BDep_self=−0.0024, BSelf−harm=−0.0018) and G9123A (BAnx_self=−0.0030, BDep_self=−0.0024, BSelf−harm=−0.0017), were found to reduce the risk of three disorders after interacting with alcohol. Sex-specific differences were also observed. In summary, the expression of mitochondrial genes could be modulated by lifestyle factors like smoking and drinking, potentially affecting psychiatric disorders. These habits might influence mitochondrial respiratory chain activity and the replication and transcriptional regulation of mitochondrial genes, culminating in changes in mitochondrial functionality and subsequently psychiatric disorders.

New Water Soluble Nickel(II) and Copper(II) Oxime Complexes Containing Acid Group: DNA Interaction Investigations

New Water Soluble Nickel(II) and Copper(II) Oxime Complexes Containing Acid Group: DNA Interaction Investigations

A Biophysics Toolbox for Reliable Data Acquisition and Processing in Integrated Force-Confocal Fluorescence Microscopy.

Integrated single-molecule force-fluorescence spectroscopy setups allow for simultaneous fluorescence imaging and mechanical force manipulation and measurements on individual molecules, providing comprehensive dynamic and spatiotemporal information. Dual-beam optical tweezers (OT) combined with a confocal scanning microscope form a force-fluorescence spectroscopy apparatus broadly used to investigate various biological processes, in particular, protein:DNA interactions. Such experiments typically involve imaging of fluorescently labeled proteins bound to DNA and force spectroscopy measurements of trapped individual DNA molecules. Here, we present a versatile state-of-the-art toolbox including the preparation of protein:DNA complex samples, design of a microfluidic flow cell incorporated with OT, automation of OT-confocal scanning measurements, and the development and implementation of a streamlined data analysis package for force and fluorescence spectroscopy data processing. Its components can be adapted to any commercialized or home-built dual-beam OT setup equipped with a confocal scanning microscope, which will facilitate single-molecule force-fluorescence spectroscopy studies on a large variety of biological systems.

New Schiff's base derivative and their nano‐sized Cr (III), Fe (III), Ru (III), and Ir (III) complexes: Preparation, DFT, characterization, bio‐catalytic, DNA interactions, cytotoxicity, and docking studies

Nano‐sized trivalent metal complexes of Cr (III), Fe (III), Ru (III), and Ir (III) were synthesized and characterized of the form [M (FMAVIEP)Cl2] where FMAVIEP = ligand (C14H11N2O2) and M = Cr (III), Fe (III), Ru (III), and Ir (III). Several spectral techniques studies were used to assess our trivalent metal complexes. The trivalent metal complexes' XRD results revealed sharp and intense diffraction peaks, signifying their crystalline properties at nanoscale particle size. Further evidence was obtained from images captured through techniques such as SEM, TEM, energy‐dispersive X‐ray, and AFM. These images confirmed the homogeneous distribution of the trivalent metal complexes over the surface of the complex. DFT studies were used to study the nano‐sized metal (III) complexes via the DFT\B3LYP computational approach, employing a 6–311G* correlation consistent basis set. The energy gap of synthesized complexes was inspected. The obtained data exhibited a strong correlation with the experimental ones, implying the bio‐efficiency of the Ru (III) complex. The absorption measurements for the nano‐sized complexes' interaction with CT‐DNA signify that nano‐sized metal (III) complexes bind through an intercalation mechanism. This conclusion is supported by the observed intrinsic binding constant (Kb) 3.33 × 105–5.84 × 105 M−1.

Co (II), Ni (II), and Cu (II) ternary complexes with 2,6‐pyridinedicarboxylic acid: Thermal decomposition, DNA interaction, and biological activity studies

Three novel ternary complexes [MII (PDA)(o‐phen)(H2O)] (MII = CoII, NiII, and CuII) were synthesized using 2,6‐pyridinedicarboxylicacid as a primary ligand and 1,10‐phenanthroline(o‐phen) as the auxiliary ligand and analyzed by FT‐IR, mass, UV–Vis, thermogravimetry analysis, and conductivity measurement data. Based on electronic spectral measurements, all three of the metal complexes were found to have octahedral stereochemistry. The way metal complexes interact with ct‐DNA was studied using various methods including absorption spectroscopy, fluorescence spectroscopy, and viscosity measurements. UV–Vis absorption technique has been used to explore the binding characteristics of M (II) complexes with ct‐DNA. The complexes bind to DNA via groove mode of binding, according to the spectral data. The salt‐dependent binding of ternary metal complexes to ct‐DNA has been studied by UV–Vis spectrophotometric titration experiment. Furthermore, gel electrophoresis is used to examine how the metal complexes interacted with the pBR322 DNA. The outcomes showed that these compounds can function as efficient DNA cleaving agents. Studies on the complexes' in vitro antibacterial activity demonstrated their importance and good antimicrobial activity at three distinct concentrations (50, 75, and 100 g/mL).

Synthesis and DNA Interactions Study of Novel Fluorinated Pyridinium Platinum (IV) Complexes with Tumor Targeting Activity

AbstractPicoplatin can effectively circumvent cisplatin‐induced resistance through the “steric hindrance effect” of its structure, but there are still problems such as toxicity and side effects, so the search for safer, more efficient platinum analogs is crucial. Here we report three fluorinated pyridine‐containing Pt(IV) complexes employing biotin as an axial ligand to provide targeting functionality. Lipid solubility studies showed that all the synthesized complexes possessed improved lipid‐water partition coefficients, which are beneficial for transmembrane transport of drugs. The DNA binding activity of the compounds was studied using UV titration, fluorescence titration, and PicoGreen staining, demonstrating the presence of potential intercalation and electrostatic interaction binding modes. It probably attributable to planar π‐π interactions provided by the aromatic pyridine ligands. Meanwhile, molecular docking studies showed that the introduction of axial biotin molecules allowed the complexes to effectively target cancer cells, which was simultaneously confirmed by the results of cellular uptake studies. And another docking result showed that the Pt(IV) complexes binds to DNA by minor groove binding. The synthesized complexes exhibited similar cytotoxicity to cisplatin in five cell lines (SW480, HCT116, HepG2, A549 and LO2), with complex 3 being superior to the parent drug, picoplatin.

Insights into the G-quadruplex DNA interaction landscape: Comparative analysis of anionic Zn(II) and Co(II) phthalocyanine-tetrasulfonate complexes.

G-quadruplexes play a pivotal role in regulating various cellular processes, including gene expression and replication, making them essential structures in understanding, and manipulating cellular functions. The development of G-quadruplex ligands holds significant promise in therapeutic and research applications, offering targeted tools to modulate G-quadruplex structures and potentially influence critical biological pathways. An exciting frontier in G-quadruplex research lies in the exploration of anionic ligands, and their profound impact on stabilizing and modulating G-quadruplex DNA. In this study, the interaction of two anionic phthalocyanine compounds (Zinc (II) phthalocyanine 3,4',4″,4‴-tetrasulfonic acid, tetrasodium salt, ZnAPC; cobalt (II) phthalocyanine 3,4',4″,4‴-tetrasulfonic acid, tetrasodium salt, CoAPC) and three separate G-quadruplex-forming DNA sequences was investigated. Interactions were carried out by DNA polymerase stop studies along with spectroscopic studies. According to the results of experimental data, it was determined that ZnAPC actively interacts with the G-quadruplex DNA structures. On the other hand, it was thought that the interaction with CoAPC was less and even occurred in simple electrostatic interactions. KD constants and Bmax constants for the interaction with ZnAPC were calculated. The KD constants for ZnAPC were found to be (1.16 ± 0.07) × 10-5, (9.75 ± .24) × 10-6 and (1.00 ± 0.36) × 10-4 M for AS1411, Vegf, and Tel21, respectively. Accordingly, it was concluded that ZnAPC interacts with G-quadruplex DNA ligands effectively.

Synthesis, antioxidant, DNA interaction, electrochemical, and spectroscopic properties of chromene-based Schiff bases: Experimental and theoretical approach

Two chromene-based Schiff base ligands were synthesized by the condensation of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde with 2-aminodiphenylamine and 1,8-diaminonaphthalene: (E)-2,2-dimethyl-6-(((2-(phenylamino)phenyl)imino)methyl)-2H-chromen-5-ol (2) and (E)-6-(((8-aminonaphthalen-1-yl)imino)methyl)-2,2-dimethyl-2H-chromen-5-ol (3). The compounds were characterized by Fourier transform infrared (FT-IR), absorption (UV-Vis) and nuclear magnetic resonance (NMR) spectroscopies, in addition to mass spectrometry (MS) analyses; the results of which were rationalized using density functional theoretical (DFT) calculations. Antioxidant activity of the Schiff bases was determined using the DPPH free radical scavenging and CUPric Ion Reducing Antioxidant Capacity (CUPRAC) assays. Compound 3 (IC50 = 14 μM) showed greater free radical scavenging ability than compound 2 (35 μM), and was also more effective than ascorbic acid and Trolox. DFT studies indicate that the HAT mechanism is favored over SET for DPPH scavenging. Both compounds exhibited stronger Cu(II) ion reducing capacity than Trolox and ascorbic acid with Trolox equivalent activity coefficient (TEAC) values of 2.0 and 1.6 for compounds 2 and 3, respectively. Furthermore, DNA cleavage and binding properties were determined using gel electrophoresis, UV-Vis spectroscopy, and cyclic voltammetry. The compounds showed copper-mediated cleavage of plasmid DNA and strong binding to DNA, with binding constants on the order of 104 M−1. The strength of DNA binding was verified by molecular docking analysis using two DNA models: a B-DNA dodecamer (-8.4 to -9.3 kcal/mol) and a hexamer (-7.8 to -7.9 kcal/mol). Overall, the chromene Schiff bases show promise as antioxidant and DNA binding agents.

Electrochemical detection of bicalutamide in sepiolite clay sensing platform: Its possible electrooxidation mechanism, determination, and DNA interaction

AbstractA carbon paste sensor was modified with sepiolite clay particles (SC/CPE) to quantify the bicalutamide (BICA). BICA's probable oxidation mechanism and the interaction between calf thymus DNA (dsDNA) were investigated (in aqueous medium, pH 4.8) for the first time. Cyclic voltammetry (CV), Electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM) were used for the investigation of surface morphology and electrochemical characteristics. The effect of the amount of SC, supporting electrolyte, and pH was optimized. Under optimum conditions, the developed sensor exhibited a linear response between 0.223 and 20.0 μM. The detection of the limit was found to be 0.069 μM. The sensor was successfully applied to quantify BICA in biological and pharmaceutical samples. Finally, cyclic voltammetry (CV) and differential pulse voltammetry (DPV) provided new insight into the interaction between BICA and ds‐DNA. The kinetic parameters for the free DNA, diffusion coefficient (D), heterogeneous rate constant (ks), and electrode surface concentration (Γ) were calculated to be 4.22×10−5 cm2 s−1, 0.57 s−1 and 7.67×10−9 mol cm−2, respectively. The (ds‐DNA)‐BICA complex parameters were 4.56×10−6 cm2 s−1, 0.70 s−1, and 1.61×10−9 mol cm−2. In addition, binding constant (K) and Gibbs free energy change (ΔG°) were 6.02×105 M−1 and −32.97 kJ mol−1, respectively.

Synthesize, structural inspection, stoichiometry in solution and DFT calculation of some novel mixed ligand complexes: DNA binding, biomedical applications and molecular docking approach

Mixed ligand chelates of Pd(II), Cu(II), VO(II), and Ag(I) with (BIP = 4,6-dimethyl-N-(octahydro-2H-benzimidazol-2-ylidene)pyrimidin-2-amine) as a main ligand and (Phen = 1, 10-phenanthroline) as a second ligand were synthesized. The recently prepared chelates were investigated through CHN analysis, (NMR, Ft-IR, Mass, and UV–Vis) spectra, magnetic moments, molar conductance, TGA, Job s methods and DFT study. The (CHN and Mass) analysis, result expose the formation of structures (1 M: 1BIP: 1Phen) chelates. The two studied ligands are established to perform in as a neutral bi-dentate approach, concluded four N2 atoms for two ligands. The study of the molar conductance indicated the non-electrolytic features for (Cu(II) and VO(II)) chelates and the electrolytic features for (Ag(I) and Pd(II)) chelates. Thermo-dynamic and Kinetics factors for various thermal degradation phases were calculated. B3LYP/LANL2DZ/6–311 g(d,p) theoretical study has been applied for estimating the MEP, FMO analysis and quantum chemical reactivity descriptors of studied molecules. Practical and computational detail reveals that BIPPCu and BIPPVO complexes possess octahedral geometry around the metal center, BIPPAg complex shows a tetrahedral configuration, and BIPPPd complex has distorted square planar geometry. In vitro anti-microbial and anti-cancer for the studied structures were applied against various strains of microbes and cancer cell lines. The results revealed that all tested chelates showed a higher activity than the free BIP. The tested complexes have been studied to antioxidant potential using DPPH study. The binding of tested chelates with DNA was studied through applying electronic absorption, gel electrophoresis as well as viscosity study, in addition to the intercalating, minor groove and electrostatic approach of DNA interacting were recommended. The studied compounds explained dynamic satisfying performing. Also, the crystal structures of DNA (PDB ID: 454D), human coronavirus Nl63 nucleocapsid protein (PDB ID: 5EPW), breast cancer protein (PDB ID: 3HB5), and Escherichia coli (PDB ID: 2VF5) was performed by molecular docking simulation. Data of docking simulation suggestions are which tested compounds have biological behavior as well as have obvious benefit in the pharmaceutical business.

Effect of Cu(II) compound containing dipicolinic acid on DNA damage: a study of antiproliferative activity and DNA interaction properties by spectroscopic, molecular docking and molecular dynamics approaches

A polymeric compound formulized as [Cu(µ-dipic)2{Na2(µ-H2O)4]n.2nH2O (I), where dipic is 2,6-pyridine dicarboxylic acid (dipicolinic acid, H2dipic), was synthesized by sonochemical irradiation. The initial in-vitro cytotoxic activity of this complex compared with renowned anticancer drugs like cisplatin, versus HCT116 colon cell lines, shows promising results. This study investigated the interaction mode between compound (I) and calf-thymus DNA utilizing a range of analytical techniques including spectrophotometry, fluorimetry, partition coefficient analysis, viscometry, gel electrophoresis and molecular docking technique. The results obtained from experimental methods reveal complex (I) could bind to CT-DNA via hydrogen bonding and van der Waals forces and the theoretical methods support it. Also, complex (I) indicates nuclease activity in the attendance of H2O2 and can act as an artificial nuclease to cleave DNA with high efficiency. Communicated by Ramaswamy H. Sarma

Novel Bis(2-cyanoacrylamide) Linked to Sulphamethoxazole: Synthesis, DNA Interaction, Anticancer, ADMET, Molecular Docking, and DFT Studies.

In the light of advancement and potential extensive use of medication design and therapy, new bis(cyanoacrylamides) incorporating sulphamethoxazole derivatives (7 a-7 f) were synthesized and confirmed by different spectral tools. In vitro anticancer activity towards different human cancer cells (HCT116, MDA-MB-231 and A549) was assessed using MTT assay. Among all derivatives, 4C- and 6C-spacer derivatives (7 e and 7 f) had the most potent growth inhibitory activities against HCT116 cells with IC50 values of 39.7 and 28.5 μM, respectively. 7 e and 7 f induced apoptosis and suppressed migration of HCT116 cells. These compounds also induced a significant increase in caspase-3 and CDH1 activities, and a downregulation of Bcl2 using ELISA. pBR322 DNA cleavage activities of cyanoacrylamides were determined using agarose gel electrophoresis. Furthermore, 7 e and 7 f showed good DNA and BSA binding affinities using different spectroscopic techniques. Furthermore, molecular docking for 7 e and 7 f was performed to anticipate their binding capabilities toward various proteins (Bcl2, CDH1 and BSA). The docking results were well correlated with those of experimental results. Additionally, density functional theory and ADMET study were performed to evaluate the molecular and pharmacokinetic features of 7 e and 7 f, respectively. Thus, this work reveals promising antitumor lead compounds that merit future research and activity enhancement.

Negative Electron Transfer Collision-Induced Dissociation of G-Quadruplexes: Uncovering the Guanine Radical Anion Loss Pathway.

G-quadruplex (G4) DNA can form highly stable secondary structures in the presence of metal cations, and research has shown its potential as a transcriptional regulator for oncogenes in the human genome. In order to explore the interactions of DNA with metal cations using mass spectrometry, employing complementary fragmentation methods can enhance structural information. This study explores the use of ion-ion reactions for sequential negative electron transfer collision-induced dissociation (nET-CID) as a complement to traditional ion-trap CID (IT-CID). The resulting nET-CID data for G4 anions with and without metal cations show an increase in fragment ion type diversity and yield of structurally informative ions relative to IT-CID. The nET-CID yields greater sequence coverage by virtue of fragmentation at the 3'-side of thymine residues, which is lacking with IT-CID. Potassium adductions to backbone fragments in IT-CID and nET-CID spectra were nearly identical. Of note is a prominent fragment resulting from a loss of a 149 Da anion seen in nET-CID of large, G-rich sequences, proposed to be radical anion guanine loss. Neutral loss of neutral guanine (151 Da) and deprotonated nucleobase loss (150 Da) have been previously reported, but this is the first report of radical anion guanine loss (149 Da). Confirmation of the identity of the 149 Da anion results from the examination of the homonucleobase sequence 5'-GGGGGGGG-3'. Loss of a charged adenine radical anion at much lower relative abundance was also noted for the sequence 5'-AAAAAAAA-3'. DFT modeling indicates that the loss of a nucleobase as a radical anion from odd-electron nucleic acid anions is a thermodynamically favorable fragmentation pathway for G.

The Therapeutic Potential in Cancer of Terpyridine-Based Metal Complexes Featuring Group 11 Elements.

Terpyridine-based complexes with group 11 metals emerge as potent metallodrugs in cancer therapy. This comprehensive review focuses on the current landscape of anticancer examples, particularly highlighting the mechanisms of action. While Cu(II) complexes, featuring diverse ancillary ligands, dominate the field, exploration of silver and gold species remains limited. These complexes exhibit significant cytotoxicity against various cancer cell lines with a commendable selectivity for non-tumorigenic cells. DNA interactions, employing intercalation and groove binding, are pivotal and finely tuned through terpyridine ligand functionalization. In addition, copper complexes showcase nuclease activity, triggering apoptosis through ROS generation. Despite silver's high affinity for nitrogen donor atoms, its exploration is relatively sparse, with indications of acting as intercalating agents causing DNA hydrolytic cleavage. Gold(III) compounds, overshadowing gold(I) due to stability concerns, not only intercalate but also induce apoptosis and disrupt the mitochondrial membrane. Further investigations are needed to fully understand the mechanism of action of these compounds, highlighting the necessity of exploring additional biological targets for these promising metallodrugs.

The ALOG domain defines a family of plant-specific transcription factors acting during Arabidopsis flower development

The ALOG (Arabidopsis LIGHT-DEPENDENT SHORT HYPOCOTYLS 1 (LSH1) and Oryza G1) proteins are conserved plant-specific Transcription Factors (TFs). They play critical roles in the development of various plant organs (meristems, inflorescences, floral organs, and nodules) from bryophytes to higher flowering plants. Despite the fact that the first members of this family were originally discovered in Arabidopsis, their role in this model plant has remained poorly characterized. Moreover, how these transcriptional regulators work at the molecular level is unknown. Here, we study the redundant function of the ALOG proteins LSH1,3,4 from Arabidopsis. We uncover their role in the repression of bract development and position them within a gene regulatory network controlling this process and involving the floral regulators LEAFY, BLADE-ON-PETIOLE, and PUCHI. Next, using in vitro genome-wide studies, we identified the conserved DNA motif bound by ALOG proteins from evolutionarily distant species (the liverwort Marchantia polymorpha and the flowering plants Arabidopsis, tomato, and rice). Resolution of the crystallographic structure of the ALOG DNA-binding domain in complex with DNA revealed the domain is a four-helix bundle with a disordered NLS and a zinc ribbon insertion between helices 2 and 3. The majority of DNA interactions are mediated by specific contacts made by the third alpha helix and the NLS. Taken together, this work provides the biochemical and structural basis for DNA-binding specificity of an evolutionarily conserved TF family and reveals its role as a key player in Arabidopsis flower development.

Multi-spectroscopic and in silico investigation of gambogic acid–calf thymus DNA interactions

Gambogic acid (GA), a xanthanoid compound, is derived from Garcinia Hanbury gamboge resin. Studying GA's DNA binding and targeting processes is crucial to understanding its tumor-targeting potentiality. This study used spectroscopic and in silico methods to investigate the GA–calf thymus DNA-binding interaction. The results of the UV–visible absorbance spectroscopy revealed that GA binds to DNA and forms a complex. Investigation of fluorescence quenching using ethidium bromide-DNA revealed that GA displaced ethidium bromide, and the type of quenching was static in nature, as determined by Stern–Volmer plot data. Thermodynamic analysis of the DNA–GA complex revealed a spontaneous, favorable interaction involving hydrogen bonding and hydrophobic interactions. Quenching experiments with potassium iodide, Acridine orange, and NaCl verified GA's groove-binding nature and the presence of weak electrostatic interactions. The thermal melting temperature of DNA in its native and bound states with GA did not differ significantly (69.27° C to 71.25° C), validating the binding of GA to the groove region. Furthermore, the groove-binding nature of GA was confirmed by studying its interaction with ssDNA and DNA viscosity. The methods of DSC, FT-IR, and CD spectroscopy have not revealed any structural aberrations in DNA bound with GA. Molecular docking and modeling studies revealed that GA has a groove-binding nature with DNA, which is consistent with prior experimental results. Finally, the findings shed information by which GA attaches to DNA and provide insights into its recognized anticancer effects via topoisomerase inhibition causing DNA cleavage, inhibition of cell proliferation and apoptosis. Communicated by Ramaswamy H. Sarma

DNA interaction, biological, and structural identification studies of bivalent nano‐sized Nickel, Palladium, and Platinum chelates of 2‐(((Z)‐6‐chloro‐3‐((E)‐([2‐hydroxyphenyl]imino)methyl)‐4H‐chromen‐4‐ylidene)amino)phenol Schiff base ligand

New nano‐sized Ni(II), Pd(II), and Pt(II) Schiff base chelates of 2‐(((Z)‐6‐chloro‐3‐((E)‐([2‐hydroxyphenyl]imino)methyl)‐4H‐chromen‐4‐ylidene)amino)phenol were designed and manufactured. The structural characterization of these isolated compounds was accomplished through spectral measurements, thermal and elemental analyses, and magnetic moment and conductivity determinations. The nano‐sized metal(II) complexes molar conductance indicated that they exhibited non‐electrolytic behavior. The UV–Vis spectral data and magnetic moment provided evidence for producing octahedral geometries in the nano‐sized complexes of Ni(II), Pd(II), and Pt(II). Metal chelates' thermal characteristics and decomposition kinetics were examined through Coats‐Redfern technique. The kinetic aspects, including pre‐exponential factor (A), the entropy of activation (ΔS), and activation energy (E) were enumerated. The X‐ray diffraction (XRD) calculations results of the trivalent metal complexes showed that sharp and intense diffraction peaks signify their crystalline properties with nanoscale particle size, and another proof was obtained from the images of SEM, TEM, EDX, and AFM also homogeneous distribution over the complex surface was confirmed. Molecular modeling techniques were adopted to optimize the metal complexes geometry. The viscosity and UV–Vis absorption determinations were utilized to assess the calf thymus DNA (CT‐DNA) interaction with the nano‐sized metal(II) chelates. The acquired data revealed that the complexes exhibit a non‐intercalative or incomplete binding pattern when interacting with DNA. The calculated DNA‐complexes binding constants are 3.93 ± 0.02 × 10,4 1.67 ± 0.3 × 105 and 2.88 ± 0.03 × 105 M−1, for nano‐sized Ni(II), Pd(II) and Pt(II) Schiff base chelates, successively. Both Gram‐negative (Escherichia coli and Pseudomonas aeruginosa) and Gram‐positive (Bacillus subtilis and Streptococcus pneumoniae) micro‐organisms were tested against H2L Schiff base ligand and its nano‐sized metal(II) complexes. Candida albicans and Aspergillus fumigatus were tested for antifungal activity, revealing that most complexes had activity lower than H2L ligand, while the complex of Ni(II) exhibited no discernible antifungal activities. Furthermore, the manufactured complexes underwent testing for their in‐vitro anticancer and antibacterial effectiveness. Furthermore, the complexes antioxidant activity was appraised through DPPH and ABTS inhibition tests, revealing distinct scavenging abilities on DPPH radicals. The complexes were ordered according to their scavenging capacity as follows: Ni(II) complex > Pd(II) complex > Pt(II) complex. Finally, the study of cell cycle arrest by the Ni(II), Pd(II), and Pt(II) complexes on HEPG2 has also been performed through flow cell cytometry.