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H‐NS, a nucleoid‐associated protein (NAP) from enterobacteria, regulates gene expression by dynamically transducing environmental cues to conformational assembly and DNA binding. In this work, we show that H‐NS from Escherichia coli, which can assemble into octameric and tetrameric oligomerization states, forms spontaneous micron‐sized liquid‐like condensates with DNA at sub‐physiological concentrations in vitro. The heterotypic condensates are metastable at 298 K, partially solubilizing with time, while still retaining their liquid‐like properties. The condensates display UCST‐like phase behavior solubilizing at higher temperatures, but with a large decrease in droplet‐assembly propensities at 310 K and at higher ionic strength. Condensate formation can be tuned in a cyclic manner between 298 and 310 K with the extent of reversibility determined by the incubation time, highlighting strong hysteresis. An engineered phospho‐mimetic variant of H‐NS (Y61E), which is dimeric and only weakly binds DNA, is unable to form condensates. The Y61E mutant solubilizes pre‐formed H‐NS condensates with DNA in a few minutes with nearly an order of magnitude speed‐up in droplet dissolution at 310 K relative to 298 K, demonstrating rapid molecular transport between dilute and condensed phases. Our results establish that the oligomerization of H‐NS is intrinsically tied not only to DNA binding but also its phase‐separation tendencies, while showcasing the regulatable and programmable nature of heterotypic condensates formed by an archetypal NAP via multiple cues and their lifetimes. [ABSTRACT FROM AUTHOR]

Chromosomal replication is a ubiquitous and essential cellular process. In bacteria, the master replication initiator DnaA plays a key role in promoting an open complex at the origin (oriC) and recruiting helicase in a tightly regulated process. The C-terminal domain IV specifically recognises consensus sequences of double-stranded DNA in oriC, termed DnaA-boxes, thereby facilitating the initial engagement of DnaA to oriC. Here, we report the 13Cβ and backbone 1H, 15N, and 13C chemical shift assignments of soluble DnaA domain IV from Bacillus subtilis at pH 7.6 and 298 K. [ABSTRACT FROM AUTHOR]

ABSTRACT Coupling the diazonium salt of sulfadiazine with dibenzoylmethane afforded the 4‐(2‐(1,3‐dioxo‐1,3‐diphenylpropan‐2‐ylidene)hydrazinyl)‐N‐(pyrimidin‐2‐yl)benzene sulfonamide ligand (HL). The ligand (HL) and its Cu(II) complex structure have been investigated via magnetic attraction testing, TGA, FTIR, UV–visible, XRD, and CHN analyses. The spectrum data indicate that the ligand demonstrates monobasic bidentate behavior via deprotonating opposite the oxygen atom of the carbonyl (CO) group and linking using the NH of the hydrazone group (NNH). Copper (II) complex present in octahedral structure. A number of TGA steps (Ea, A, ΔH*, ΔS*, and ΔG*) had their dynamical characteristics computed and described using the Coats–Redfern and Horowitz–Metzger formulas. Molecular studio programmer was utilized to perform density functional theory (DFT) calculations in order to investigate the ideal configuration of HL and its Cu(II) complex. The HL and its copper (II) complex exhibited antitumor effects against MCF‐7 and HepG‐2 cell lines. Furthermore, the width of the inhibition zone was employed to evaluate the in vitro antibacterial effect of HL and a specific complex towards Gram‐negative organisms Escherichia coli (E. coli) and Gram‐positive organisms Staphylococcus aureus. The ligand and its Cu(II) complex were examined using both the viscosity and spectrum of absorption of calf thymus DNA binding experiments. [ABSTRACT FROM AUTHOR]

FOXP2 is a transcription factor associated with speech and language. Like other FOX transcription factors, it has a DNA binding region called the forkhead domain (FHD). This domain can exist as a monomer or a domain swapped dimer. In addition to the FHD, the leucine zipper region (LZ) of FOXP2 is also believed to be associated with both DNA binding and oligomerization. To better understand the relationship between DNA binding and oligomerization of FOXP2, we investigated its structure, stability and dynamics, focusing specifically on the FHD and the LZ. We did this by using two constructs: one containing the isolated FHD and one containing both the LZ and the FHD (LZ‐END). We demonstrate in this work, that while the FHD maintains a monomeric form that is capable of binding DNA, the LZ‐END undergoes a dynamic transition between oligomeric states in the presence of DNA. Our findings suggest that FOXP2's LZ domain influences DNA binding affinity through a change in oligomeric state. We show through hydrogen exchange mass spectroscopy that certain parts of the FHD and interlinking region become less dynamic when in the presence of DNA, confirming DNA binding and oligomerization in these regions. Moreover, the detection of a stable equilibrium intermediate state during LZ‐END unfolding supports the idea of cooperation between these two domains. Overall, our study sheds light on the interplay between two FOXP2 domains, providing insight into the protein's ability to respond dynamically to DNA, and enriching our understanding of FOXP2's role in gene regulation. [ABSTRACT FROM AUTHOR]

The dimeric nuclear factor kappa B (NF-κB) transcription factors (TFs) regulate gene expression by binding to a variety of κB DNA elements with conserved G:C-rich flanking sequences enclosing a degenerate central region. Toward defining mechanistic principles of affinity regulated by degeneracy, we observed an unusual dependence of the affinity of RelA on the identity of the central base pair, which appears to be noncontacted in the complex crystal structures. The affinity of κB sites with A or T at the central position is ~10-fold higher than with G or C. The crystal structures of neither the complexes nor the free κB DNAs could explain the differences in affinity. Interestingly, differential dynamics of several residues were revealed in molecular dynamics simulation studies, where simulation replicates totaling 148 μs were performed on NF-κB: DNA complexes and free κB DNAs. Notably, Arg187 and Arg124 exhibited selectivity in transient interactions that orchestrated a complex interplay among several DNA-interacting residues in the central region. Binding and simulation studies with mutants supported these observations of transient interactions dictating specificity. In combination with published reports, this work provides insights into the nuanced mechanisms governing the discriminatory binding of NF-κB family TFs to κB DNA elements and sheds light on cancer pathogenesis of cRel, a close homolog of RelA. [ABSTRACT FROM AUTHOR]

Objective: A series of new 7-methoxytetrahydropyrrolo[3,4-a]carbazole-1,3-diones derivatives (VIa–VIc) modified with hydroxyl-alkyl side chains have been synthesized and examined their biological activity. Based on their interaction with the DNA of the calf thymus (CT), the side chain effect on their ability to bind DNA was assessed and their cytotoxicity was assessed. Methods: The DNA-binding properties were studied by absorption spectroscopy, EB-DNA displacement, circular dichroism, viscosity, and thermal denaturation measurements. The anticancer activities of (VIa–VIc) were evaluated on different cell lines A549, HepG2, and K562. Results and Discussion: The experimental evidences indicated that compounds could interact with CT-DNA through intercalation into the base pairs of DNA. Compound (VIc) exhibited utmost DNA binding propensity and cytotoxicity compared to the compounds (VIa) and (VIb). The intrinsic binding constant values for compounds (VIa–VIc) were 1.0 × 104, 0.372 × 104, and 2.14 × 105 M–1 respectively, suggesting side chains plays a key role in DNA binding affinity. Conclusions: We talked about their structure and the relevance to bioactivity. Compound (VIc) has stronger cytotoxic action and more efficient DNA binding in similar experimental settings. [ABSTRACT FROM AUTHOR]

Four complexes of essential metal ions, Cu(II) and Ni(II), with the new sulfonamide ligand N-(pyridin-2-ylmethyl)quinoline-8-sulfonamide (HQSMP) were synthesized and physicochemically and structurally characterized. Complex [Cu(QSMP)Cl]n (2) consists of a polymeric chain formed by distorted square pyramidal units. In 2, the sulfonamide ligand acts as a bridge coordinating to one Cu(II) through its three N atoms and to another metal ion via one O atom in the sulfonamido group, while the pentacoordinate complex [Cu(QSMP)(C6H5COO)] (3) presents a highly distorted square pyramidal geometry. Complex [Ni(QSMP)(C6H5COO)(CH3OH)][Ni(QSMP)(CH3COO)(CH3OH)] (4) consists of two mononuclear entities containing different anion coligands, either a benzoate or an acetate group. Both units exhibit a distorted octahedral geometry. The interaction of the complexes with CT-DNA was studied by means of UV-Vis and fluorescence spectroscopy, interestingly revealing that the Ni(II) complex presents the highest affinity towards the nucleic acid. Complexes 1 and 2 are able to cleave DNA. Both compounds show promising nuclease activity at relatively low concentrations by mediating the production of a reactive oxygen species (ROS). The interaction of the four complexes with bovine serum albumin (BSA) was also investigated, showing that the compounds can bind to serum proteins. The antitumor potential of complexes 1 and 2 was evaluated against the A549 lung adenocarcinoma cell line, revealing cytotoxic properties that were both dose- and time-dependent. [ABSTRACT FROM AUTHOR]

Forkhead box P2 (FOXP2) regulates expression of various genes and is associated with language, speech and neural development as well as cancer. Since there may be a putative link between sex and language and because transcription factors rarely function in isolation, this study aims to investigate whether FOXP2 directly associates with oestrogen receptor α (ER1), a nuclear receptor responsible for sexual differentiation that is also associated with cancer. Isothermal titration calorimetry and fluorescence anisotropy were used to investigate the interaction between the DNA-binding forkhead domain (FHD) of FOXP2, the N-terminal region (NT) of FOXP2, and the ligand-binding domain (LBD) of ER1. ER1 LBD does not interact with FOXP2 NT but associates with apo-FOXP2 FHD in an enthalpically favourable manner. The affinity of this interaction is inversely correlated to the salt concentration. Additionally, FOXP2 FHD that is bound to ER1 LBD, has reduced ability to interact with its cognate DNA. This research identifies a novel interaction between ER1 LBD and FOXP2 FHD and shows that the interaction is regulated by salt. Moreover, FOXP2 FHD cannot bind to both ER1 LBD and DNA simultaneously, suggesting that this interaction could be involved in regulating the transcriptional pathway of FOXP2 should the interaction be found in vivo. This study could serve as a foundation for uncovering the basis of sexual dimorphism in speech and language development and related disorders and potentially offers an alternate for targeted cancer therapies. • A novel interaction is identified in vitro between FOXP2 FHD and ER1 LBD. • This interaction has both an electrostatic and hydrophobic interface and involves the DNA-binding Helix 3 of FOXP2 FHD. • The ligand binding region and the LXXLL-binding AF-2 region of ER1 LBD is not involved in the protein-protein interaction. • FOXP2 FHD can bind either to DNA or to ER1 but not to both simultaneously. • The identified FOXP2-ER1 interaction could be involved in regulating FOXP2's transcriptional activity. [ABSTRACT FROM AUTHOR]

Cystobactamids are aromatic oligoamides that exert their natural antibacterial properties by inhibition of bacterial gyrases. Such aromatic oligoamides were proposed to inhibit α‐helix‐mediated protein‐protein interactions and may serve for specific recognition of DNA. Based on this suggestion, we designed new derivatives that have duplicated cystobactamid triarene units as model systems to decipher the specific binding mode of cystobactamids to double stranded DNA. Solution NMR analyses revealed that natural cystobactamids as well as their elongated analogues show an overall bent shape at their central aliphatic unit, with an average CX‐CY‐CZ angle of ~110 degrees. Our finding is corroborated by the target‐bound structure of close analogues, as established by cryo‐EM very recently. Cystobactamid CN‐861‐2 binds directly to the bacterial gyrase with an affinity of 9 μM, and also exhibits DNA‐binding properties with specificity for AT‐rich DNA. Elongation/dimerization of the triarene subunit of native cystobactamids is demonstrated to lead to an increase in DNA binding affinity. This implies that cystobactamids' gyrase inhibitory activity necessitates not just interaction with the gyrase itself, but also with DNA via their triarene unit. [ABSTRACT FROM AUTHOR]

Abstract The mitochondria are central in the cellular response to changing environmental conditions resulting from disease states, environmental exposures or normal physiological processes. Although the influences of environmental stressors upon the nuclear epigenome are well characterized, the existence and role of the mitochondrial epigenome remains contentious. Here, by quantifying the mitochondrial epigenomic response of pineal gland cells to circadian stress, we confirm the presence of extensive cytosine methylation within the mitochondrial genome. Furthermore, we identify distinct epigenetically plastic regions (mtDMRs) which vary in cytosinic methylation, primarily in a non CpG context, in response to stress and in a sex-specific manner. Motifs enriched in mtDMRs contain recognition sites for nuclear-derived DNA-binding factors (ATF4, HNF4A) important in the cellular metabolic stress response, which we found to be conserved across diverse vertebrate taxa. Together, these findings suggest a new layer of mito-nuclear interaction in which the nuclear metabolic stress response could alter mitochondrial transcriptional dynamics through the binding of nuclear-derived transcription factors in a methylation-dependent context.

GOLDEN2‐LIKE (GLK) transcription factors belong to the GARP superfamily and are known as major positive regulators of greening in various plants, including Arabidopsis, rice, maize, tomato, and moss. Recent studies have reported many GLK downstream targets and binding partners. This revealed the breadth of GLK‐related downstream pathways and its multiplexed‐regulatory system beyond greening regulation. To evaluate the complexity of the molecular mode of action of GLKs, here we summarize the current knowledge of the interactions from promoters of direct GLK downstream target genes involved in chlorophyll biosynthesis, photosystem I, photosystem II, catechin biosynthesis, flowering, and abscisic acid signaling, and proteins that directly bind to GLKs, including kinases, E3 ligases, repressors of GLK activity, histone deacetylases, transcriptional coregulators, and transcription factors. This overview of GLK‐related pathways supports the pleiotropic function of GLKs as core regulators of a multi‐regulatory system involving plant greening and other phenotypes. [ABSTRACT FROM AUTHOR]

Novel metal complexes of nickel(II), copper(II) and zinc(II) have been synthesized and characterized. DFT‐based molecular orbital energy calculations of the synthesized ligand and metal complexes have been studied. Ligand and its complexes were screened for their antibacterial activities by disk diffusion method. The quantitative antimicrobial activity of the test compounds was evaluated using Resazurin based Microtiter Dilution Assay. The interaction of these complexes with Herring sperm DNA (HS-DNA) was analyzed via UV–Visible absorption, circular dichroism and Voltammetric studies, which indicates that these complexes bind to HS-DNA by intercalation binding mode. Molecular docking was also used to identify the interaction between ligand and complexes with DNA. α-Amylase inhibition activity of ligand its metal complexes has been determined by DNS method. Kinetic studies were carried out to identify the mode of inhibition using Lineweaver-Burk plot. The cytotoxicity of these metal complexes has been evaluated by MTT assay against normal 3T3L1 cells. [ABSTRACT FROM AUTHOR]

ABSTRACTAll life forms have evolved to respond appropriately to various environmental and internal cues. In the animal kingdom, the prototypical regulator class of such cellular responses is the Rel homology domain proteins including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Fungi, the close relatives of animals, have also evolved with their own NF-κB-like regulators called velvet family proteins to govern cellular and chemical development. Here, we conducted a detailed investigation of the taxonomic broad presence of velvet proteins. We observed that velvet proteins are widely distributed in the fungal kingdom. Moreover, we have identified and characterized 21 major velvet clades in fungi. We have further revealed that the highly conserved velvet domain is composed of three distinct motifs and acts as an evolutionarily independent domain, which can be shuffled with various functional domains. Such rearrangements of the velvet domain have resulted in the functional and type diversity of the present velvet regulators. Importantly, our in-deep analyses of the primary and 3D structures of the various velvet domains showed that the fungal velvet domains can be divided into two major clans: the VelB and the VosA clans. The 3D structure comparisons revealed a close similarity of the velvet domain with many other eukaryotic DNA-binding proteins, including those of the Rel, Runt, and signal transducer and activator of transcription families, sharing a common β-sandwich fold. Altogether, this study improves our understanding of velvet regulators in the fungal kingdom.IMPORTANCEFungi are the relatives of animals in Opisthokonta and closely associated with human life by interactive ways such as pathogenicity, food, and secondary metabolites including beneficial ones like penicillin and harmful ones like the carcinogenic aflatoxins. Similar to animals, fungi have also evolved with NF-κB-like velvet family regulators. The velvet proteins constitute a large protein family of fungal transcription factors sharing a common velvet domain and play a key role in coordinating fungal secondary metabolism, developmental and differentiation processes. Our current understanding on velvet regulators is mostly from Ascomycota fungi; however, they remain largely unknown outside Ascomycota. Therefore, this study performed a taxonomic broad investigation of velvet proteins across the fungal kingdom and conducted a detailed analysis on velvet distribution, structure, diversity, and evolution. The results provide a holistic view of velvet regulatory system in the fungal kingdom.

With the increase in drug-resistant bacteria, new antibacterial drugs have emerged as a prominent area of research and development. Antimicrobial peptides (AMPs), as innate immune agents, have garnered significant attention due to their potent, rapid, and broad-spectrum antibacterial activity. This study focused on investigating the functionality of three AMPs (CATH 1, CATH 2, and MAP34-B) derived from goat submandibular glands. Among these AMPs, CATH 2 and MAP34-B exhibited direct antibacterial activity against both Gram-negative and Gram-positive bacteria, primarily targeting the bacterial membrane. Additionally, these two AMPs were found to have the potential to induce reactive oxygen species (ROS) production in bacterial cells and interact with bacterial genome DNA, which may play a crucial role in their mechanisms of action. Furthermore, both CATH 1 and CATH 2 demonstrated significant antioxidant activity, and all three AMPs exhibited potential anti-inflammatory activity. Importantly, the cytotoxic activity of these AMPs against mammalian cells was found to be weak, and their hemolytic activity was extremely low. Overall, the characteristics of these three AMPs found in goat submandibular glands offer new insights for the study of host protection from an immunological perspective. They hold promise as potential candidates for the development of novel antibacterial agents, particularly in the context of combating drug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Transcription factor binding to a gene regulatory region induces or represses its expression. Binding and expression target analysis (BETA) integrates the binding and gene expression data to predict this function. First, the regulatory potential of the factor is modeled based on the distance of its binding sites from the transcription start sites in a decay function. Then the differential expression statistics from an experiment where this factor was perturbed represent the binding effect. The rank product of the two values is employed to order in importance. This algorithm was originally implemented in Python. We reimplemented the algorithm in R to take advantage of existing data structures and other tools for downstream analyses. Here, we attempted to replicate the findings in the original BETA paper. We applied the new implementation to the same datasets using default and varying inputs and cutoffs. We successfully replicated the original results. Moreover, we showed that the method was appropriately influenced by varying the input and was robust to choices of cutoffs in statistical testing. [ABSTRACT FROM AUTHOR]

The mitochondria are central in the cellular response to changing environmental conditions resulting from disease states, environmental exposures or normal physiological processes. Although the influences of environmental stressors upon the nuclear epigenome are well characterized, the existence and role of the mitochondrial epigenome remains contentious. Here, by quantifying the mitochondrial epigenomic response of pineal gland cells to circadian stress, we confirm the presence of extensive cytosine methylation within the mitochondrial genome. Furthermore, we identify distinct epigenetically plastic regions (mtDMRs) which vary in cytosinic methylation, primarily in a non CpG context, in response to stress and in a sex-specific manner. Motifs enriched in mtDMRs contain recognition sites for nuclear-derived DNA-binding factors (ATF4, HNF4A) important in the cellular metabolic stress response, which we found to be conserved across diverse vertebrate taxa. Together, these findings suggest a new layer of mito-nuclear interaction in which the nuclear metabolic stress response could alter mitochondrial transcriptional dynamics through the binding of nuclear-derived transcription factors in a methylation-dependent context. [ABSTRACT FROM AUTHOR]

In drug development, it is very important to study the physicochemical properties of drugs under various solution conditions in order to understand their mechanism of action and their interactions with bioactive compounds. In this regard, this study attempts to elucidate the effects of co-solvent and co-solute on the physicochemical properties of Montelukast sodium and its possible interactions with deoxyribonucleic acid (DNA). The physicochemical, volumetric and thermodynamic properties of Montelukast sodium were determined by various measurements such as density, viscosity and surface tension. Most of these measured parameters responded differently when ethanol (co-solvent) and sodium chloride (co-solvent) were added to the drug solution, and/or when the concentration and temperature of the drug solution were changed. Various solution properties such as flow behavior, surface activity and association behavior of Montelukast sodium were also affected by the addition of DNA. UV–Vis spectroscopy was also used to better understand the qualitative and quantitative strength of DNA-drug interactions in water. Using UV–Visible analysis, the Montelukast DNA binding constant (Kb) was determined to be 6.861 × 103 (L Mol−1). Physicochemical and spectroscopic results confirmed that there may be physicochemical type interactions between the drug and DNA. It is also proposed that hydrogen bonding can occur between the oxygen and hydrogen atoms of the Montelukast sodium and the hydrogen, oxygen and nitrogen atoms of the DNA molecule. [ABSTRACT FROM AUTHOR]

Three new Co (II), Ag (I), and Cd (II) ion complexes were created from the ligand, 2-(phenylglycyl)-N-(p-tolyl)hydrazine-1-carbothioamide (H2LB). The structural makeup of the new compounds was clarified using analytical and spectroscopic techniques. Then, using the Gaussian09 software, geometry optimization was done for each synthesis. Furthermore, the compound's antibacterial and anticancer properties were evaluated against different types of bacteria and the HepG2 cell line using non-irradiated and irradiated complexes, where the complex (A1) is higher than them. It was proposed that only an intercalation or replacement technique was used when the ligand and complexes [Co(H2L)(NO3)2]H2O (B1, A1) interacted with CT-DNA. Calculations were made for the intrinsic binding constant Kb. According to a molecular docking study, the ligands and complexes revealed fascinating interactions with the amino acids in the ribosyltransferase active site. (Code: 3GEY).

Transcription factor binding to a gene regulatory region induces or represses its expression. Binding and expression target analysis (BETA) integrates the binding and gene expression data to predict this function. First, the regulatory potential of the factor is modeled based on the distance of its binding sites from the transcription start sites in a decay function. Then the differential expression statistics from an experiment where this factor was perturbed represent the binding effect. The rank product of the two values is employed to order in importance. This algorithm was originally implemented in Python. We reimplemented the algorithm in R to take advantage of existing data structures and other tools for downstream analyses. Here, we attempted to replicate the findings in the original BETA paper. We applied the new implementation to the same datasets using default and varying inputs and cutoffs. We successfully replicated the original results. Moreover, we showed that the method was appropriately influenced by varying the input and was robust to choices of cutoffs in statistical testing.

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 Kb 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. [ABSTRACT FROM AUTHOR]

Several kinds of anticancer drugs are presently commercially accessible, but low efficacy, solubility, and toxicity have reduced the overall therapeutic indices. Thus, the search for promising anticancer drugs continues. The interactions of numerous essential anticancer drugs with DNA are crucial to their biological functions. Here, the anticancer effects of N-ethyl toluene-4-sulphonamide (8a) and 2,5-Dichlorothiophene-3-sulphonamide (8b) on cell lines from breast and cervical cancer were investigated. The study also compared how these substances interacted with the hearing sperm DNA. The most promising anticancer drug was identified as 2,5-Dichlorothiophene-3-sulfonamide (8b), which showed GI50 of 7.2 ± 1.12 µM, 4.62 ± 0.13 µM and 7.13 ± 0.13 µM against HeLa, MDA-MB231 and MCF-7 cells, respectively. Moreover, it also exhibited significant electrostatic and non-electrostatic contributions to the binding free energy. The work utilized computational techniques, such as molecular docking and molecular dynamic (MD) simulations, to demonstrate the strong cytotoxicity of 2,5-Dichlorothiophene-3-sulfamide (8b) in comparison to standard Doxorubicin and cisplatin, respectively. Molecular docking experiments provided additional support for a role for the minor groove in the binding of the 2,5-Dichlorothiophene-3-sulfamide (8b)-DNA complex. The molecular docking studies and MD simulation showed that both compounds revealed comparable inhibitory potential against standard Doxorubicin and cisplatin. This study has the potential to lead to the discovery of new bioactive compounds for use in cancer treatment, including metallic and non-metallic derivatives of 2,5-Dichlorothiophene-3-sulfonamide (8b). It also emphasizes the worth of computational approaches in the development of new drugs and lays the groundwork for future research. [ABSTRACT FROM AUTHOR]

• Synthesis of novel mononuclear and homodinuclear Ru(II) complexes. • Synthesis of novel mixed trinuclear Ru(II)/Ru(III) complex. • Sstructures elucidateion the by UV-Vis, Near InfraRed spectroscopy, NMR, ESI-Mass and cyclic voltammetry techniques. • Investigating phrancological performance of the complexes. • Performing molecular docking studies on the DNA-interaction with the complexs. Three new heteroleptic ruthenium(II) complexes with mixed ligands were prepared: [Ru(bpy) 2 (Cl 2 dpq)]Cl 2 (1), [Ru(bpy) 2 (Cl 2 dpq)Ru(bpy) 2 ]Cl 4 (2), and [Ru(bpy) 2 (Cl 2 dpq)RuCl 2 (Cl 2 dpq)Ru(bpy) 2 ]Cl 5 (3), in which Cl 2 dpq = 6,7-dichloro-2,3-di(pyridin-2-yl)quinoxaline; bpy = 2,2′-bipyridine. Various physicochemical tools were used to characterize the new complexes, such as elemental analysis, infrared, 1H-NMR and ESI-MS. The complexes were investigated for their Photochemical properties by studying their UV-Vis, luminescence, and NIR spectra. Additionally, cyclic voltammetry studies were performed to evaluate the electrochemical behavior of the complexes. Investigation of the new complexes' interaction with calf thymus DNA (CT-DNA) was carried out using various spectroscopic techniques and the experimental data were corroborated against molecular docking studies. Furthermore, the complexes' in vitro cytotoxicity against DPPH radicals and their scavenging effects against HeLa and MCF-7 cell lines were assessed. [Display omitted] [ABSTRACT FROM AUTHOR]

• Flexible π extension benefits the groove binding with DNA. • Both covalent and non-covalent interactions with DNA exist. • DNA pocket docking should consider the total electronic effect. • Crystal structure was highly overlapped with the DFT-optimized structure. • The "Off-On" character helps us to understand the tumor therapeutic target. Organometallic medicines based on ruthenium (Ru) have attracted interest as chemotherapeutic and bioimaging agents due to their low toxicity and superior physical optical characteristics. However, there are still no ideal candidates in clinical trials due to the lack of understanding of the structure-activity relationships (SARs) of polypyrodyl Ru(II) complexes. Though increasing the electron-donating ability of the ligands has been proven to benefit bioactivity due to the fast hydroxylation rate between chlorine and DNA, the total electronic effects are much more important, especially for the binding modes between Ru(II)-polypyridyl complexes and DNA. By evaluating the electron-donating ability of the ligand complexes 1 - 4 through density functional theory (DFT) calculations, bioactivities tests, and docking studies, we investigated the relationship between the structures of Ru(II) complexes and cytotoxicity. Our findings showed that it was insufficient to merely consider the impact of electron-donating effects on biological activities in place of interaction modes. Furthermore, the cellular imaging study investigated the complex with phenyl substituents (1) and confirmed that the main target was DNA. Besides, the "off-on" emission phenomena of complex 1 indicated that there is also covalent interaction with DNA. These findings offer valuable insight into the development of SARs of polypyrodyl Ru(II) complexes. The flexible π extension benefit the fits of Ru(II) complex adopted with DNA, which enhance the cytotoxicity of antitumor effects. [Display omitted] [ABSTRACT FROM AUTHOR]

H-NS, a nucleoid-associated protein (NAP) from enterobacteria, regulates gene expression by dynamically transducing environmental cues to conformational assembly and DNA binding. In this work, we show that H-NS from Escherichia coli, which can assemble into octameric and tetrameric oligomerization states, forms spontaneous micron-sized liquid-like condensates with DNA at sub-physiological concentrations in vitro. The heterotypic condensates are metastable at 298 K, partially solubilizing with time, while still retaining their liquid-like properties. The condensates display UCST-like phase behavior solubilizing at higher temperatures, but with a large decrease in droplet-assembly propensities at 310 K and at higher ionic strength. Condensate formation can be tuned in a cyclic manner between 298 and 310 K with the extent of reversibility determined by the incubation time, highlighting strong hysteresis. An engineered phospho-mimetic variant of H-NS (Y61E), which is dimeric and only weakly binds DNA, is unable to form condensates. The Y61E mutant solubilizes pre-formed H-NS condensates with DNA in a few minutes with nearly an order of magnitude speed-up in droplet dissolution at 310 K relative to 298 K, demonstrating rapid molecular transport between dilute and condensed phases. Our results establish that the oligomerization of H-NS is intrinsically tied not only to DNA binding but also its phase-separation tendencies, while showcasing the regulatable and programmable nature of heterotypic condensates formed by an archetypal NAP via multiple cues and their lifetimes., (© 2024 The Protein Society.)

HMGB1 is a dual-function protein that acts as a chromatin-binding protein and as a danger-associated molecular pattern (DAMP) when released from activated immune cells or injured tissue. In much of the HMGB1 literature, immunomodulatory effects of extracellular HMGB1 are proposed to depend on its oxidation state. However, many of the foundational studies for this model have been retracted or flagged with expressions of concern. The literature on HMGB1 oxidation reveals a diversity of redox proteoforms of HMGB1 that are inconsistent with current models of redox modulation regulating HMGB1 secretion. A recent study of acetaminophen toxicity has identified previously unrecognized HMGB1 oxidized proteoforms. HMGB1 undergoes oxidative modifications that could serve as pathology-specific biomarkers and drug targets.

The RelEB3 toxin–antitoxin (TA) system of Salmonella enterica subsp. enterica serovar Typhimurium consists of a RelE3 toxin which suppresses bacterial growth, but its RelB3 antitoxin does not neutralise the toxin. The relEB3 operon is widespread in Proteobacteria and is related to higBA2 from Vibrio cholerae. In contrast to the ribosome-dependent HigB2 toxin, however, the RelE3 toxin degraded free RNA independently of the ribosome. A basic loop possibly involved in HigB2's binding to the ribosome is shortened in RelE3, which instead contains a uniquely conserved R51 important for RelE3's toxicity. The RelB3 antitoxin, meanwhile, specifically recognised the CACC T GGTG palindromic motif in the promoter site. RelB3 contains a unique P14 which is conserved as Ala in most homologues, and mutating P14 to Ala enabled the antitoxin to bind to RelE3 and restored bacterial growth. The P14 RelB3 variant, which most likely arose by a point mutation in a recent ancestor of S. Typhimurium and closely related serovars, could have possibly provided the bacteria with a faster response to stress, and might have spread to other serovars through homologous recombination. • The antitoxin of the RelEB3 toxin–antitoxin system does not neutralise the toxin. • The RelE3 toxin suppressed growth by cleaving RNA independently of the ribosome. • The RelB3 antitoxin recognised the CACC T GGTG palindromic motif. • The P14A mutation restored RelB3's ability to bind RelE3 and neutralise it. • P14 RelB3 might speed up stress response and spread by homologous recombination. [ABSTRACT FROM AUTHOR]

Genomic compaction is an essential characteristic of living organisms. Nucleoid-associated proteins (NAPs) are a group of small proteins that play crucial roles in chromosome architecture and affect DNA replication, transcription, and recombination by imposing topological alterations in genomic DNA, thereby modulating global gene expression. EbfC/YbaB was first described as a DNA-binding protein of Borrelia burgdorferi that regulates the expression of surface lipoproteins with roles in virulence. Further studies indicated that this protein binds specifically and non-specifically to DNA and colocalises with nucleoids in this bacterium. The data showed that this protein binds to DNA as a homodimer, although it can form other organised structures. Crystallography analysis indicated that the protein possesses domains responsible for protein–protein interactions and forms a "tweezer" structure probably involved in DNA binding. Moreover, sequence analysis revealed conserved motifs that may be associated with dimerisation. Structural analysis also showed that the tridimensional structure of EbfC/YbaB is highly conserved within the bacterial domain. The DNA-binding activity was observed in different bacterial species, suggesting that this protein can protect DNA during stress conditions. These findings indicate that EbfC/YbaB is a broadly distributed NAP. Here, we present a review of the existing data on this NAP. [ABSTRACT FROM AUTHOR]

Ni (II) and Co (II) complexes of thiosemicarbazide ligand (2‐(anilinoacetyl)‐N‐(3‐methylphenyl)hydrazine‐1‐carbothioamide(H2LB) have been prepared and characterized by 1HNMR, IR, elemental analyses, molar conductance, UV–visible spectra, magnetic susceptibility measurements, thermogravimetric analysis (TGA/DTG), and X‐ray differaction pattern before and after irradiation. The results confirmed that gamma rays enhanced the stability of irradiated compounds compared with those non‐irradiated. Density functional theory (DFT) calculations of synthesized compounds were completely optimized with respect to the energy using B3LYP level. DNA binding of compounds before and after gamma irradiation has been studied. Inhibitory effect on the growth of bacteria against gram‐positive (Streptococcus pyogenes) and gram‐negative (Escherichia coli) of synthesized compounds have been investigated. The results revealed that Ni (II) complex after gamma irradiation showed a higher antibacterial activity against gram positive and gram negative bacteria more than all investigated compounds. The ability of scavenging 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) free radical by our synthesized compounds was investigated on the basis of the determination of IC50 values. [ABSTRACT FROM AUTHOR]

Cancer disease is developing all over the world mainly in developing countries. We should learn more about DNA–ligand interactions to design new drugs that target biological activities like transcription, replication and translation of particular genes. To understand the mechanism of action and design-specific DNA binders, the evaluation of DNA–ligand interactions is critical. Novel barbituric acid derivatives based on (benzyloxy)benzaldehydes were synthesized and evaluated as DNA-binding agents. Among products, molecular docking studies revealed that 4j and 4m have the best interactions with the ctDNA via the minor groove binding. These results were approved by the quantum mechanics calculations. The interaction profiles of the selected compound (4j and 4m) with DNA were evaluated by UV–Visible titration. UV–Visible titration data confirm this interaction. According to the molecular modeling results, the Structure–Activity relationships for all synthesized barbituric acid derivatives were proposed. It was observed that N,N-dimethyl barbituric acid/4-hydroxybenzaldehyde derivatives have better DNA interactions than barbituric acid/vanillin and barbituric acid/3-hydroxybenzaldehyde derivatives. [ABSTRACT FROM AUTHOR]

Several metal diimine complexes have been reported to possess anticancer properties. To evaluate the anticancer properties of tetrahedral zinc(II) diimine complexes, six complexes were synthesized with the general formula M(N^N)Cl2 {where M = Zn, Pt and N^N = 2,2’-biquinoline (1), 2,2’-dipyridylketone (2) and 4-((pyridine-2-ylmethylene)amino)phenol (3)}. In general, the intrinsic DNA-binding constants for the different compounds exhibited values within close proximity; the changes in the viscosity of the CT-DNA upon binding to the compounds suggest intercalation-binding mode. Molecular docking study predicted that complexes containing the highly planar ligand 2,2’-biquinoline are capable to establish π–π interactions with nucleobases of the DNA; the other four complexes engaged in donor–acceptor interactions with DNA nucleobases. The six complexes and two reference drugs (cisplatin and sunitinib) were tested against two cancer cell lines (COLO 205 and RCC-PR) and one normal cell line (LLC-MK2), highlighting the better performance of the zinc(II) complexes compared to their platinum(II) analogues. Moreover, zinc(II) complexes have higher selectivity index values than the reference drugs, with promising anticancer properties.

[Display omitted] • Photophysical properties for fluorenyl corroles were investigated; • ROS and photostability properties of fluorenyl corroles were investigated; • DNA and BSA-binding properties was explored in the corrole derivatives; In this study, it was evaluated the photophysical, electrochemical, photobiological, and DNA/BSA-binding properties of fluorenyl corrole derivatives H 3 MFluCor and H 3 TFluCor. Absorption and emission analyses were corroborated by theoretical calculations performed using time-dependent density functional theory, which revealed natural transition orbitals densities concentrated around the tetrapyrrolic macrocycle in all cases. The experimental studies indicated that the corroles H 3 MFluCor and H 3 TFluCor are stable in solution and exhibited photostability primarily in DMSO(5%)/Tris-HCl (pH 7.4) buffer. The generation of reactive oxygen species (ROS) and log P OW values highlight their potential application in photobiological methods, as these corroles effectively generate ROS with more lipophilic characteristics. Furthermore, their binding capacity towards double-stranded DNA and bovine serum albumin (BSA) was also evaluated by spectroscopic techniques and molecular docking calculations. The interactive profile with biomolecules indicates that the corrole derivatives H 3 MFluCor and H 3 TFluCor tend to binding into the minor grooves of DNA through secondary forces, which are particularly pronounced at site III of the BSA, likely due to the static interactions. [ABSTRACT FROM AUTHOR]

Synthesis and structural characterization of nano crystallites of bis-violurate-based manganese(II) and copper(II) chelates is the subject of the present study. Analytical data and mass spectra as well as thermal analysis determined the molecular formulas of the present metal chelates. Spectroscopic and magnetic measurements assigned the structural formula of the present violurate metal complexes. The spectroscopic and magnetic investigations along with structural analysis results indicated the square planar geometry of both the Mn(II) and Cu(II) complexes. The structural analysis of the synthesized metal complexes was achieved by processing the PXRD data using specialized software Expo 2014. Spectrophotometeric and viscosity measurements showed that violuric acid and its Mn(II) and Cu(II) complexes successfully bind to DNA with intrinsic binding constants Kb from 38.2 × 105 to 26.4 × 106 M−1. The antiviral activity study displayed that the inhibitory concentrations (IC50) of SARS-CoV-2 by violuric acid and its Mn(II) and Cu(II) complexes are 84.01, 39.58 and 44.86 μM respectively. Molecular docking calculations were performed on the SARS-CoV-2 virus protein and the computed binding energy values are −0.8, −3.860 −5.187 and −4.790, kcal/mol for the native ligand, violuric acid and its Mn(II) and Cu(II) complexes respectively. Insights into the relationship between structures of the current compounds and their degree of reactivity are discussed.

Researchers use ChIP binding data to identify potential transcription factor binding sites. Similarly, they use gene expression data from sequencing or microarrays to quantify the effect of the transcription factor overexpression or knockdown on its targets. Therefore, the integration of the binding and expression data can be used to improve the understanding of a transcription factor function. Here, we implemented the binding and expression target analysis (BETA) in an R/Bioconductor package. This algorithm ranks the targets based on the distances of their assigned peaks from the transcription factor ChIP experiment and the signed statistics from gene expression profiling with transcription factor perturbation. We further extend BETA to integrate two sets of data from two transcription factors to predict their targets and their combined functions. In this article, we briefly describe the workings of the algorithm and provide a workflow with a real dataset for using it. The gene targets and the aggregate functions of transcription factors YY1 and YY2 in HeLa cells were identified. Using the same datasets, we identified the shared targets of the two transcription factors, which were found to be, on average, more cooperatively regulated.

• A tridentate schiff base ligand containing naphtyl moiety with general formula (N^N^OH) was synthesized. • Pt-L2 was obtained from the ligand with the formula [PtCl(N^N^O)]. • Changes in the relative viscosity of ct-DNA indicated an intercalation mode of binding for Pt-L2. • Pt-L2 indicated the spontaneous formation of an adduct with BSA with good binding affinity. • Pt-L2 possesses better IC 50 values compared to cisplatin against two cancer cell lines. A tridentate Schiff base ligand was synthesized via the reaction of 2-hydroxynpthaldehyd with N -phenyl-o-phenylenediamine. The obtained ligand was utilized in synthesizing Pt-L2 [PtCl(N^N^O)]. The ligand and Pt-L2 were characterized by IR, NMR and mass spectroscopies as well as elemental analysis. The DNA-binding of Pt-L2 was examined by fluorescence quenching using the EB-DNA adduct method. The apparent affinity for the compound toward ct-DNA was nearly twice the affinity of ethidium bromide. Changes in the relative viscosity induced by platinum complexes of ct-DNA indicated an intercalation mode of binding for Pt-L2 and covalent binding for the second platinum compound, Pt-L1, synthesized from 3-ethoxysalicyaldehyde and N -phenyl-o-phenylenediamine. BSA-binding by Pt-L2 indicated the spontaneous formation of an adduct with the protein with good binding affinity (7.7 × 104). The anticancer activities of Pt-L2 were evaluated against two cancer cell lines and compared to that of Pt-L1 and cisplatin. Pt-L2 has better IC 50 values, possibly because of its highly π-delocalized planar system. Moreover, selectivity index for Pt-L2 is high (SI = 168) which is one of the criteria for potential chemotherapeutic agents (higher than that observed for cisplatin (SI = 37)). [Display omitted] [ABSTRACT FROM AUTHOR]

Six new Pd(II) and Ir(III) thiazole-based complexes were synthesized and characterized by EA, ICP, FTIR, TGA-MS and SEM-EDX. In order to evaluate the biological activity of the synthesized compounds CT-DNA binding was studied and moreover ligands, complexes were tested against cancer cell lines. [Display omitted] Thiazoles and their derivatives are one of the most active classes of compounds known for their wide spectrum of bioactivity. Metal complexes, based on them, show antitumor potential that is attractive for investigations. Herein, we report 6 new biologically active thiazole-based complexes have been synthesized. The iridium- and palladium-based coordination compounds obtained by the precipitation method were characterized using elemental analysis (EA), Fourier-transform infrared spectroscopy (FTIR), magnetic measurements, thermogravimetric analysis coupled with mass spectrometry (TGA-MS), and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX). Spectroscopic data helped to propose the formulas of the complexes and indicated that all ligands acted in a monodentate manner. Water molecules were identified by thermal analysis and FTIR spectroscopy. Mathematical analysis and evaluation of thermodynamic parameters including entropy (ΔS), Gibbs free energy (ΔG), and activation energy (E) were performed using the Coats–Redfern method for all complexes. The biological potential (anticancer, antibacterial, and antifungal properties) of compounds was analyzed by biological evaluation studies. Investigated CT-DNA studies revealed that the prepared compounds were intercalatively bound to the DNA. Cytotoxicity analyses showed that complexation with Ir(III) increased the toxicity of L2 towards both tested cell lines (LN-229 and MDA-MB-231), while complexation of L3 with Pd(II) significantly increased cytotoxic activity against LN-229. Due to this, the further biological studies, such as apoptosis/necrosis detection, cell cycle analysis and JC-1 fluorescence measurements were performed on this pair of compounds. [ABSTRACT FROM AUTHOR]

[Display omitted] • New benzhydrazone based Schiff base metal(II) complexes were synthesized and characterized. • DNA binding experiments revealed complexes bind to DNA through the intercalation binding mode. • DNA cleavage investigation displayed Cu(II) complexes completely destroy the DNA instead of cleavage. • Ni(II) complex has (IC 50 2.38 ± 2.2 µg/mL) a strong ability to inhibit the growth of MCF-7 cell line. Bivalent mononuclear transition metal complexes of cobalt, nickel, copper and zinc were synthesized from (E)-2-(1-(2-(2-hydroxybenzoyl)hydrazono)ethoxy)benzoic acid. The FTIR, 1H NMR, 13C NMR, HR-Mass, UV–Vis., EPR, Powder XRD and SEM analysis were employed to investigate the structural features of synthesized compounds. The spectral data confirmed the square planar geometry of the complexes. The EPR spectra of the Cu(II) complex supported the proposed geometry. Powder X-ray diffraction (PXRD) analysis and scanning electron microscopy (SEM) imaging revealed that the complexes consist of nano-sized grains exhibiting a polycrystalline structure. The in vitro antimicrobial efficacy of the compounds was evaluated against various bacterial and fungal strains using the well diffusion method. The in vitro antibacterial activity demonstrated that all synthesized compounds were biologically active, and Zn(II) complex exhibited the highest inhibitory activity against S. aureus (gram-positive bacteria). For antioxidant activity, the free ligand and its metal chelates were evaluated using the standard DPPH method, revealing that the Co(II) complex displayed least inhibitory concentration value (IC 50 = 16 ± 2.3 μg/mL) indicating the highest antioxidant activity. DNA interaction studies showed intercalation between complexes and DNA, and the Cu(II) complex exhibited a higher binding affinity of 2.78 ± 0.34 × 105 M−1. The DNA cleavage ability of the compounds was assessed using gel electrophoresis, demonstrating the effective cleavage of the pBR322 plasmid DNA. The Schiff base and its complexes were subjected to an anticancer evaluation against the human breast cancer cell line (MCF-7) using the MTT assay method. The percentage cell inhibition of the compounds was calculated. [ABSTRACT FROM AUTHOR]

The DNA-binding AT-rich interactive domain (ARID) exists in a wide range of proteins throughout eukaryotic kingdoms. ARID domain-containing proteins are involved in manifold biological processes, such as transcriptional regulation, cell cycle control and chromatin remodeling. Their individual domain composition allows for a sub-classification within higher mammals. ARID is categorized as binder of double-stranded AT-rich DNA, while recent work has suggested ARIDs as capable of binding other DNA motifs and also recognizing RNA. Despite a broad variability on the primary sequence level, ARIDs show a highly conserved fold, which consists of six α-helices and two loop regions. Interestingly, this minimal core domain is often found extended by helices at the N- and/or C-terminus with potential roles in target specificity and, subsequently function. While high-resolution structural information from various types of ARIDs has accumulated over two decades now, there is limited access to ARID-DNA complex structures. We thus find ourselves left at the beginning of understanding ARID domain target specificities and the role of accompanying domains. Here, we systematically summarize ARID domain conservation and compare the various types with a focus on their structural differences and DNA-binding preferences, including the context of multiple other motifs within ARID domain containing proteins. [ABSTRACT FROM AUTHOR]

Pyrazine and its derivatives are a large group of compounds that exhibit broad biological activity, the changes of which can be easily detected by a substituent effect or a change in the functional group. The present studies combined theoretical research with the density functional theory (DFT) approach (B3LYP/6-311+G**) and experimental (potentiometric and spectrophotometric) analysis for a thorough understanding of the structure of chlorohydrazinopyrazine, its physicochemical and cytotoxic properties, and the site and nature of interaction with DNA. The obtained results indicated that 2-chloro-3-hydrazinopyrazine (2Cl3HP) displayed the highest affinity to DNA. Cytotoxicity studies revealed that the compound did not exhibit toxicity toward human dermal keratinocytes, which supported the potential application of 2Cl3HP in clinical use. The study also attempted to establish the possible equilibria occurring in the aqueous solution and, using both theoretical and experimental methods, clearly showed the hydrophilic nature of the compound. The experimental and theoretical results of the study confirmed the quality of the compound, as well as the appropriateness of the selected set of methods for similar research. [ABSTRACT FROM AUTHOR]

A porphyrinoid containing cis‐diol pyrroline subunit and fused nitro‐quinoxaline π‐elongated unit at its peripheral β,β'‐positions was prepared. The UV‐visible spectrum exhibits typical chlorin‐like sharp Qy‐band, but significantly more red‐shifted (687 nm) and more intense than for a normal diol chlorin. The precursor porphyrin exhibited weak Q‐bands slightly above 650 nm. The same porphyrin exhibited a low pH dependent ∼40 nm red‐shift in its UV‐visible spectrum. Analysis of the frontier molecular orbital energies using electrochemical techniques and theoretical analysis of the lowest energy geometry of the porphyrin confirmed the roles of non‐planar conformation and electronic charge redistribution in inducing this spectral feature. In addition, biophysical and computational analysis of DNA‐binding behavior of these porphyrinoids indicated that groove binding induced by Van der Waals contacts was the preferred mode of interaction. [ABSTRACT FROM AUTHOR]

Vanadium compounds have been set in various fields as anticancer, anti-diabetic, anti-parasitic, anti-viral, and anti-bacterial agents. This study reports the synthesis and structural characterization of oxidovanadium(IV)-based imidazole drug complexes by the elemental analyzer, molar conductance, magnetic moment, spectroscopic techniques, as well as thermal analysis. The obtained geometries were studied theoretically using density functional theory (DFT) under the B3LYP level. The DNA-binding nature of the ligands and their synthesized complexes has been studied by the electronic absorption titrations method. The biological studies were carried with in-vivo assays and the molecular docking method. The EPR spectra asserted the geometry around the vanadium center to be a square pyramid for metal complexes. The geometries have been confirmed using DFT under the B3LYP level. Moreover, the quantum parameters proposed promising bioactivity of the oxidovanadium(IV) complexes. The results of the DNA-binding revealed that the investigated complexes bind to DNA via non-covalent mode, and the intrinsic binding constant (Kb) value for the [VO(SO4)(MNZ)2] H2O complex was promising, which was 2.0 × 106 M−1. Additionally, the cytotoxic activity of the synthesized complexes exhibited good inhibition toward both hepatocellular carcinoma (HepG-2) and human breast cancer (HCF-7) cell lines. The results of molecular docking displayed good correlations with experimental cytotoxicity findings. Therefore, these findings suggest that our synthesized complexes can be introduced as effective anticancer agents. [ABSTRACT FROM AUTHOR]