Potential DNA Binding Research Articles

Mechanisms of SSBP1 variants in mitochondrial disease: Molecular dynamics simulations reveal stable tetramers with altered DNA binding surfaces

Several mutations in the gene for the mitochondrial single stranded DNA binding protein (SSBP1) have recently been implicated in human disease, but initial reports are insufficient to explain the molecular mechanism of disease, including the possible role of SSBP1 heterotetramers in heterozygous patients. Here we employed molecular simulations to model the dynamics of wild type and 31 variant SSBP1 tetramer systems, including 7 variant homotetramer and 24 representative heterotetramer systems. Our simulations indicate that all variants are stable and most have stronger intermonomer interactions, reduced solvent accessible surface areas, and a net loss of positive surface charge. We then used structural alignments and phosphate binding simulations to predict DNA binding surfaces on SSBP1. Our models suggest that nearly the entire surface of SSBP1, excluding flexible loops and protruding helices, is available for DNA binding, and we observed several potential DNA binding hotspots. Changes to the protein surface in variant SSBP1 tetramers potentially alter anchor points or wrapping paths, rather than abolishing binding altogether. Overall, our findings disqualify tetramer destabilization or gross disruption of DNA binding as mechanisms of disease. Instead, they are consistent with subtle changes to DNA binding, wrapping, or release that cause rare but consequential failures of mtDNA maintenance, which, in turn, are consistent with the late onset of disease in most of the reported SSBP1 cases.

Genome-wide regulation of CpG methylation by ecCEBPα in acute myeloid leukemia

Background: Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by genetic and epigenetic aberrations that alter the differentiation capacity of myeloid progenitor cells. The transcription factor CEBPα is frequently mutated in AML patients leading to an increase in DNA methylation in many genomic locations. Previously, it has been shown that ecCEBPα (extra coding CEBP α) - a lncRNA transcribed in the same direction as CEBPα gene - regulates DNA methylation of CEBPα promoter in cis. Here, we hypothesize that ecCEBPα could participate in the regulation of DNA methylation in trans.Method: First, we retrieved the methylation profile of AML patients with mutated CEBPα locus from The Cancer Genome Atlas (TCGA). We then predicted the ecCEBPα secondary structure in order to check the potential of ecCEBPα to form triplexes around CpG loci and checked if triplex formation influenced CpG methylation, genome-wide.Results: Using DNA methylation profiles of AML patients with a mutated CEBPα locus, we show that ecCEBPα could interact with DNA by forming DNA:RNA triple helices and protect regions near its binding sites from global DNA methylation. Further analysis revealed that triplex-forming oligonucleotides in ecCEBPα are structurally unpaired supporting the DNA-binding potential of these regions. ecCEBPα triplexes supported with the RNA-chromatin co-localization data are located in the promoters of leukemia-linked transcriptional factors such as MLF2.Discussion: Overall, these results suggest a novel regulatory mechanism for ecCEBPα as a genome-wide epigenetic modulator through triple-helix formation which may provide a foundation for sequence-specific engineering of RNA for regulating methylation of specific genes.

Synthesis, structure, DNA/protein molecular docking and biological studies of hydrazone ligand derived Cu(II) and VO(IV) complexes

In this study, Cu(II) (1) and VO(IV) (2) complexes are synthesized from hydrazones, HL1=(E)-N′-(2-hydroxy-3,5-diiodobenzylidene)-4-tert-butylbenzohydrazide and HL2=(E)-N′-(3-bromo-5-chloro-2-hydroxybenzylidene)-4-tert-butylbenzohydrazide and are well characterized by the way of different spectroscopic and analytical techniques. The chemical structure of complexes 1 and 2 is confirmed by single crystal X-ray crystallography studies. The molecular docking studies are carried out to better comprehend the preferential mode of binding of these compounds against biomecular targets such as DNA and plasma protein (HSA). Complex 1 revealed the lowest ACE value (−503.36 kcal/mol), suggests that the potential DNA binding efficacy of complex 1 is being stronger than the other compounds of interest. Besides, complexes 1 and 2 displayed better binding affinities with HSA protein molecules relative to their respective parent hydrozone ligands. These results have been reflected as their significant antibacterial and antifungal activities.

Delila-PY, a Pipeline for Utilizing the Delila Suite of Software to Identify Potential DNA Binding Motifs.

Predicting potential DNA binding motifs is a critical part of understanding gene expression across all domains of life. Here, we report the development of Delila-PY, an easy-to-use pipeline for utilizing the Delila suite of software to identify DNA binding motifs.

Genome-wide regulation of CpG methylation by ecCEBPα in acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by genetic and epigenetic aberrations that alter the differentiation capacity of myeloid progenitor cells. The transcription factor CEBPα is frequently mutated in AML patients leading to an increase in DNA methylation in many genomic locations. Previously, it has been shown that ecCEBPα (extra coding CEBP α) - a lncRNA transcribed in the same direction as CEBPα gene - regulates DNA methylation of CEBPα promoter in cis. Here, we hypothesize that ecCEBPα could participate in the regulation of DNA methylation in trans. Method: First, we retrieved the methylation profile of AML patients with mutated CEBPα locus from The Cancer Genome Atlas (TCGA). We then predicted the ecCEBPα secondary structure in order to check the potential of ecCEBPα to form triplexes around CpG loci and checked if triplex formation influenced CpG methylation, genome-wide. Results: Using DNA methylation profiles of AML patients with a mutated CEBPα locus, we show that ecCEBPα could interact with DNA by forming DNA:RNA triple helices and protect regions near its binding sites from global DNA methylation. Further analysis revealed that triplex-forming oligonucleotides in ecCEBPα are structurally unpaired supporting the DNA-binding potential of these regions. ecCEBPα triplexes supported with the RNA-chromatin co-localization data are located in the promoters of leukemia-linked transcriptional factors such as MLF2. Discussion: Overall, these results suggest a novel regulatory mechanism for ecCEBPα as a genome-wide epigenetic modulator through triple-helix formation which may provide a foundation for sequence-specific engineering of RNA for regulating methylation of specific genes.

DeepGRN: prediction of transcription factor binding site across cell-types using attention-based deep neural networks

BackgroundDue to the complexity of the biological systems, the prediction of the potential DNA binding sites for transcription factors remains a difficult problem in computational biology. Genomic DNA sequences and experimental results from parallel sequencing provide available information about the affinity and accessibility of genome and are commonly used features in binding sites prediction. The attention mechanism in deep learning has shown its capability to learn long-range dependencies from sequential data, such as sentences and voices. Until now, no study has applied this approach in binding site inference from massively parallel sequencing data. The successful applications of attention mechanism in similar input contexts motivate us to build and test new methods that can accurately determine the binding sites of transcription factors.ResultsIn this study, we propose a novel tool (named DeepGRN) for transcription factors binding site prediction based on the combination of two components: single attention module and pairwise attention module. The performance of our methods is evaluated on the ENCODE-DREAM in vivo Transcription Factor Binding Site Prediction Challenge datasets. The results show that DeepGRN achieves higher unified scores in 6 of 13 targets than any of the top four methods in the DREAM challenge. We also demonstrate that the attention weights learned by the model are correlated with potential informative inputs, such as DNase-Seq coverage and motifs, which provide possible explanations for the predictive improvements in DeepGRN.ConclusionsDeepGRN can automatically and effectively predict transcription factor binding sites from DNA sequences and DNase-Seq coverage. Furthermore, the visualization techniques we developed for the attention modules help to interpret how critical patterns from different types of input features are recognized by our model.

DNA threading intercalation of enantiopure [Ru(phen)2bidppz]2+ induced by hydrophobic catalysis.

The enantiomers of a novel mononuclear ruthenium(ii) complex [Ru(phen)2bidppz]2+ with an elongated dppz moiety were synthesized. Surprisingly, the complex showed no DNA intercalating capability in an aqueous environment. However, by the addition of water-miscible polyethylene glycol ether PEG-400, self-aggregation of the hydrophobic ruthenium(ii) complexes was counter-acted, thus strongly promoting the DNA intercalation binding mode. This mild alteration of the environment surrounding the DNA polymer does not damage or alter the DNA structure but instead enables more efficient binding characterization studies of potential DNA binding drugs.

Mononuclear copper(i) complexes of triphenylphosphine and N,N′-disubstituted thioureas as potential DNA binding chemotherapeutics

Herein, nine copper(i) bromide complexes with N,N′-disubstituted thioureas and triphenylphosphine, were synthesized via a simple solution-based reaction at 60 °C and characterized, selected complexes were screened for DNA binding.

Correction: Mononuclear copper(i) complexes of triphenylphosphine and N,N′-disubstituted thioureas as potential DNA binding chemotherapeutics

Correction for ‘Mononuclear copper(i) complexes of triphenylphosphine and N,N′-disubstituted thioureas as potential DNA binding chemotherapeutics’ by Syed Ishtiaq Khan et al., New J. Chem., 2021, 45, 8925–8935, DOI: 10.1039/D0NJ06182D.

Yb/Chitosan Catalyzed Synthesis of Highly Substituted Piperidine Derivatives for Potential Nuclease Activity and DNA Binding Study.

Herein, a new chitosan-supported ytterbium nano-catalyst has been prepared and used in a mild, efficient, and expeditious method for the synthesis of substituted piperidine derivatives via threecomponent condensation of substituted anilines, formaldehyde and different cyclic/acyclic active methylene compounds at room temperature. The catalyst was characterized by FTIR, XRD, SEM, EDX, TEM, ICP-AES and the stability of the catalyst was evaluated by TG analysis. The synthesized compound 3,3,11,11-Tetramethyl-15-(phenyl)-15- azadispiro[5.1.5.3]hexadecane-1,5,9,13-tetrone (3a) was explored for pBR322 DNA cleavage activity and genotoxicity. Further, the interaction of 3a with CT-DNA was investigated through UV-vis, fluorescence and viscosity. The preparation of Yb/chitosan nano-catalyst was verified and the catalyst was found effective towards substituted piperidine formations with the catalyst reusability. Compound 3a was successfully tested for DNA cleavage activity. In addition, fluorescence results revealed that compound 3a interacted with DNA with a binding affinity of 4.84 x 104 M-1. Our findings suggest that compounds bearing spiro-piperidine scaffold, synthesized using reusable nano-catalyst, could be effective biological agents.

Role of the DNA Binding Activity of Herpes Simplex Virus 1 VP22 in Evading AIM2-Dependent Inflammasome Activation Induced by the Virus.

AIM2 is a cytosolic DNA sensor of the inflammasome, which induces critical innate immune responses against various invading pathogens. Earlier biochemical studies showed that the binding of AIM2 to DNA triggered the self-oligomerization of AIM2, which is essential for AIM2 inflammasome activation. We recently reported that VP22, a virion tegument protein of herpes simplex virus 1 (HSV-1), inhibited activation of the AIM2 inflammasome in HSV-1-infected cells by preventing AIM2 oligomerization. VP22 binds non-specifically to DNA; however, its role in HSV-1 replication is unclear. We investigated the role of VP22 DNA binding activity in the VP22-mediated inhibition of AIM2 inflammasome activation. We identified a VP22 domain encoded by amino acids 227 to 258 as the minimal domain required for its binding to DNA in vitro Consecutive alanine substitutions in this domain substantially impaired the DNA binding activity of VP22 in vitro and attenuated the inhibitory effect of VP22 on AIM2 inflammasome activation in an AIM2 inflammasome reconstitution system. The inhibitory effect of VP22 on AIM2 inflammasome activation was completely abolished in macrophages infected with a recombinant virus harboring VP22 with one of the consecutive alanine substitutions, similar to the effect of a VP22-null mutant virus. These results suggested that the DNA binding activity of VP22 is critical for VP22-mediated AIM2 inflammasome activation in HSV1-infected cells.IMPORTANCE VP22, a major component of the HSV-1 virion tegument, is conserved in alphaherpesviruses and has structural similarity to ORF52, a component of the virion tegument that is well-conserved in gammaherpesviruses. Although the potential DNA binding activity of VP22 was discovered decades ago, its significance in the HSV-1 life cycle is poorly understood. Here, we show that the DNA binding activity of VP22 is critical for the inhibition of AIM2 inflammasome activation induced in HSV-1-infected cells. This is the first report to show a role for the DNA binding activity of VP22 in the HSV-1 life cycle, allowing the virus to evade AIM2 inflammasome activation, which is critical for its replication in vivo.

CBIO-12. THE ROLES OF lncRNAs IN GBM RADIATION RESISTANCE AND TUMOR RECURRENCE

Abstract Glioblastoma multiforme (GBM) almost invariably recurs and tumors exhibit resistance to conventional therapies. One mechanism of resistance is enhanced DNA damage response (DDR) to alkylating chemotherapy or radiation therapy (RT). We have generated 8 novel GBM patient-derived xenograft (PDX) models of tumor recurrence following serial in vivo irradiation (6 x 2Gy fractions over 2 weeks for 6+ rounds). RNA sequencing has revealed enrichment of a number of DDR pathways in the RT selected (RTS) PDX. Differential enrichment across the RTS PDX suggests multiple molecular routes to acquired RT resistance. We have also identified differential enrichment of molecular signatures for cell cycle progression, stemness, and chromatin remodeling all suggesting decreased proliferation, increased stemness, and more compacted chromatin states associated with RTS PDX. We have identified altered kinase signaling in RTS PDX that may suggest targetable signaling pathways using small molecule inhibitors. Integrated ‘–omics’ analysis has identified SRC family kinases and altered expression of collagens related to the RTS profile. Long non-coding RNAs (lncRNA) have the potential to regulate molecular phenotypes through nucleic acid binding. We have identified 269 lncRNAs significantly differentially expressed in the RTS condition. We have determined that a number of these transcripts have DNA binding potential in gene regulatory regions proximal to kinase, DDR, cell cycle, stemness, and chromatin remodeling genes. Analysis of lncRNAs and genes proximal to their binding sites has revealed regulatory networks potentially governing cell fate and phenotype. We have observed complex correlations of some of these transcripts, such as ZFAS1, which has a positive correlation with expression of stemness-promoting genes and simultaneous inverse correlation with cell cycle genes. This suggests ZFAS1 could be a phenotypic switch between a RT-sensitive proliferating cell and a RT-resistant non-proliferating stem-like cell. LncRNAs may represent a novel therapeutic target for the treatment of therapy resistant, recurrent GBM.

DNA binding and antiradical potential of ethyl pyruvate: Key to the DNA radioprotection

DNA is the store house of all necessary hereditary information for growth of cells and tissues. Physiological functionality of DNA depends on its 3D helical structure and any distortion in a structure may lead to mutation and genomic instability that may translate into disease like cancer. In order to prevent DNA damage, an exogenous compound is required that can either scavenge the excess free radicals or enhance the structural integrity of DNA through binding. In the present study, the binding mechanism of ethyl pyruvate (EP) with DNA models using different spectroscopic techniques was investigated for their structural integrity. Besides, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays were performed to determine the antioxidant scavenging of EP. Plasmid DNA relaxation assay was performed to assess the radioprotection efficacy of EP in the plasmid DNA. Circular dichroism (CD) and UV–Vis absorbance spectroscopic data confirmed the conformation change in ctDNA upon binding with EP. The molecular docking visualized that EP stacks between the DNA bases with a glide score of −2.117 kcalmol while EP binds in the minor groove region of DNA with the glide score of −1.414 kcalmol . DPPH and FRAP data confirmed that EP scavenges significantly radicals at higher concentrations. In vitro radioprotection study in plasmid DNA pBR322 showed that EP retained the supercoiled form of plasmid DNA at 50 Gy radiation dose.

Design, efficient synthesis, docking studies, and anticancer evaluation of new quinoxalines as potential intercalative Topo II inhibitors and apoptosis inducers

As an extension for our earlier effort in the field of discovery of anticancer agents acting on DNA and Topo II, eighteen quinoxaline derivatives were designed and synthesized. Such members were designed to possess the main essential pharmacophoric features of DNA intercalators. The cytotoxic potential of the synthesized compounds was assessed against a group of human cancer cell lines (HCT-116, HepG2, and MCF-7). Doxorubicin as potential intercalative Topo II inhibitor, was used as a positive reference. In general, compounds 12, 15, 19, 21, and 22 showed promising anti-proliferative activities against the three cell lines with IC50 values ranging from 2.81 to 10.23 µM. The cytotoxicities of the most active compounds against normal human cells (WI-38) were evaluated, and the results revealed that these compounds have low toxicity. Further examination for the most active anti-proliferative members as Topo II inhibitors was also performed, showing a narrow range of the inhibitory activities (from 0.45 to 1.06 µM). In addition, DNA/methyl green assay was carried out to evaluate DNA-binding potential of such compounds. The results indicated that these compounds have strong to moderate DNA-binding affinities ranging from 33.48 to 51.23 µM. Further studies exhibited the capability of compound 22 to induce apoptosis in HepG2 cells and can arrest growth of such cells at G2/M phase. Also, compound 22 produced a significant increase in the level of caspase- 3 (10 folds) and caspase-9 (7 folds) compared to the control cells. Molecular docking studies were also conducted to investigate possible binding interactions between the target compounds and the DNA-Topo II complex.

Geochemical identification of potential DNA-hotspots and DNA-infrared fingerprints in lake sediments

DNA preserved in sedimentary materials can be used to study past ecosystem changes, such as species' colonization and extinction. It is believed that minerals, especially clay minerals, enhance the preservation of DNA. However, the role of minerals, as well as organic matter, on DNA sorption in heterogeneous sediments is still not clear. In this study, we examined the effect of mineral and organic matter on DNA binding in lake sediments. Bulk and size-fractionated sediments (0–4, 4–16, 16–64, and >64 μm), having different mineral and organic composition, were used to test DNA sorption; similar experiments were also run after the removal of sedimentary organic matter. Additionally, diffuse reflectance infrared spectroscopy (DRIFT) was used to determine the chemical changes caused by DNA sorption and subsequently produce a DNA-infrared (IR) fingerprint. Clay minerals were the main minerals to sorb DNA in the different samples. Moreover, mica promoted DNA sorption in all size fractions, while chlorite promoted DNA sorption in size fractions greater than 16 μm; clay-mineral and organo-mineral complexes caused a preference of certain clay minerals over others. Sedimentary organic matter affected DNA sorption by covering as well as by amplifying potential DNA binding sites, yet DNA sorption did not change significantly. DNA sorption showed IR spectral modifications mainly at ~1640, 1416, and 1231 cm−1. Interestingly, the DNA-IR fingerprint in the heterogeneous sediments was evident by those peaks after spectral subtraction. Finally, we proposed a simple model, based on sediment geochemistry, that can be used to determine potential DNA-hotspots in sediments.

Evaluation of Antioxidant, Anticancer and DNA Binding Potentials of Noble Metal Nanoparticles Synthesized Using Aristolochia indica and Indigofera tinctoria

The deployment of biological resources for the synthesis of nanoparticles of metals and metal oxides is the latest addition to green chemistry. The present work describes the use of aqueous stem extracts of Aristolochia indica and Indigofera tinctoria for the synthesis of silver and gold nanoparticles (Ag and Au NPs). The synthesized NPs were characterized by UV–Vis., FT-IR, TEM, XRD and EDAX analyzes. The antioxidant activities of functionalized Ag and Au NPs were studied by the DPPH method and the nanoparticles showed greater antioxidant activity than that of the extract; AgNPs synthesized by A. indica showed antioxidant activity of 84%. The in vitro cytotoxicity of the Ag and Au NPs was assessed by the MTT assay method using the HeLa cell line and the NPs synthesized by A. indica showed nearly 100% toxicity. DNA binding capacity was investigated using calf thymus-DNA by UV–Vis spectra, the hyperchromism shift inferred the groove binding of nanoparticles and the binding constants (1.66 × 107 and 1.06 × 107 and 0.77 × 107 and 1.59 × 107 M−1 for the NPs of Ag and Au synthesized by A. indica and I. tinctoria respectively) indicate a high potential of these nanoparticles for the administration of drugs.

Synthesis of Dihydrazones as Potential Anticancer and DNA Binding Candidates: A Validation by Molecular Docking Studies.

Accounting for mortality nearly one in four of human and second highest leading cause of death worldwide. Every year, about 10 million new cancers are diagnosed and causing major health issues in both developing and developed countries. A series of new dihydrazones were synthesized and screened for in vitro anticancer activity against three different MDA-MB-231, A546 and MCF7 cell lines and validated by DNA binding and molecular docking approaches. In the present investigations, synthesized compounds 21, 22, 23 and 24 exhibited potent anticancer activity against tested cancer cell lines and DNA binding study using methyl green comparing to Doxorubicin and ethidium bromide as a positive control respectively. The Structure Activity Relationship (SAR) showed that the electron withdrawing groups (-Cl, -NO2, - F, and -Br) favored the DNA binding studies and anticancer activity whereas, electron donating groups (-OH and - OCH3) showed moderate activity. In the molecular docking study, binding interactions of the most active compounds 21, 22, 23 and 24 stacked with A-T rich regions of the DNA minor groove by surface binding interactions were confirmed. Further, the tuning of active analogs for targeted therapy was warranted.

Biophysical characterisation of DNA origami nanostructures reveals inaccessibility to intercalation binding sites

Intercalation of drug molecules into synthetic DNA nanostructures formed through self-assembled origami has been postulated as a valuable future method for targeted drug delivery. This is due to the excellent biocompatibility of synthetic DNA nanostructures, and high potential for flexible programmability including facile drug release into or near to target cells. Such favourable properties may enable high initial loading and efficient release for a predictable number of drug molecules per nanostructure carrier, important for efficient delivery of safe and effective drug doses to minimise non-specific release away from target cells. However, basic questions remain as to how intercalation-mediated loading depends on the DNA carrier structure. Here we use the interaction of dyes YOYO-1 and acridine orange with a tightly-packed 2D DNA origami tile as a simple model system to investigate intercalation-mediated loading. We employed multiple biophysical techniques including single-molecule fluorescence microscopy, atomic force microscopy, gel electrophoresis and controllable damage using low temperature plasma on synthetic DNA origami samples. Our results indicate that not all potential DNA binding sites are accessible for dye intercalation, which has implications for future DNA nanostructures designed for targeted drug delivery.

Synthesis, X-ray crystal structure elucidation and Hirshfeld surface analysis of N-((4-(1H-benzo[d]imidazole-2-yl)phenyl)carbamothioyl)benzamide: investigations for elastase inhibition, antioxidant and DNA binding potentials for biological applications.

The interest in the present study pertains to the development of a new compound based upon a benzimidazole thiourea moiety that has unique properties related to elastase inhibition, free radical scavenging activity and its DNA binding ability. The title compound, N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-3-benzoyl thiourea (C21H18N4O2SH2O:TUBC), was synthesized by reacting an acid chloride of benzoic acid with potassium thiocyanate (KSCN) along with the subsequent addition of 4-(1H-benzo[d]imidazol-2-yl)benzenamine via a one-pot three-step procedure. The structure of the resulting benzimidazole based thiourea was confirmed by spectroscopic techniques including FTIR, 1H-NMR, 13C-NMR and single crystal X-ray diffraction and further examined by Hirshfeld surface analysis. TUBC was also investigated by using both in silico methodology including molecular docking for elastase inhibition along with quantum chemical studies and in vitro experimental methodology utilizing elastase inhibition and free radical scavenging assay along with DNA binding experiments. Docking results confirmed that TUBC binding was within the active region of elastase. In comparison to the reference drug oleanolic acid, the low IC50 value of TUBC also indicated its high tendency towards elastase inhibition. TUBC scavenged 80% of DPPH˙ radicals which pointed towards its promising antioxidant activity. TUBC–DNA binding by DFT, docking, UV-visible spectroscopy and viscosity measurements revealed TUBC to be a potential drug candidate that binds spontaneously and reversibly with DNA via a mixed binding mode. All theoretical and experimental findings pointed to TUBC as a potential candidate for a variety of biological applications.

Structural and Biological Studies on Transition Metal Complexes of 4-Aminoantipyrine Derivative

Novel tetra dentate Cu(II), Ni(II), Co(II), VO(II) and Zn(II) Schiff base complexes have been synthesized from salicylidene-4-iminoantipyrine and tyrosine. The synthesized Schiff base complexes was characterized by powder X-ray diffraction studies (XRD), scanning electron microscopy (SEM), FT-IR, ESR, 1H NMR, 13C NMR, UV-vis, molar conductance and magnetic susceptibility measurements. The general formula of complexes was confirmed as [ML] type [M = Cu(II), Co(II), Zn(II), Ni(II) and VO(II); L = C27H24N4O4]. Magnetic susceptibility, IR and UV-vis, spectral data showed that all the complexes have square planar geometry except vanadyl complex which suggests square pyramidal geometry. Lower molar conductance values proved that all the chelates were non-electrolytic nature. The X-band ESR spectra of [CuL] and [VOL] complexes in DMSO solution suggest that the complexes were predominant covalent character. Powder XRD and SEM image pattern evidenced that all the compounds were crystalline in nature and their size ranges from 100-40 nm. Calf thymus DNA binding potential of [CuL] and [VOL] complexes shows that the binding occurs through intercalation mode with low binding constant. The analgesic, CNS, antiulcer and antimicrobial activities of the investigated compounds report reveals that the chelates were significant effect than free Schiff base.