Uridine Bisphosphonates Differentiate Phosphoglycosyl Transferase Superfamilies.

Complex bacterial glycoconjugates drive interactions between pathogens, symbionts, and their human hosts. Glycoconjugate biosynthesis is initiated at the membrane interface by phosphoglycosyl transferases (PGTs), which catalyze the transfer of a phosphosugar from a soluble uridine diphosphosugar (UDP-sugar) substrate to a membrane-bound polyprenol-phosphate (Pren-P). The two distinct superfamilies of PGT enzymes (polytopic and monotopic) show striking differences in their structure and mechanism. We designed and synthesized a series of uridine bisphosphonates (UBPs), wherein the diphosphate of the UDP and UDP-sugar is replaced by a substituted methylene bisphosphonate (CXY-BPs; X/Y = F/F, Cl/Cl, (S)-H/F, (R)-H/F, H/H, CH3/CH3). UBPs and UBPs incorporating an N-acetylglucosamine (GlcNAc) substituent at the ß-phosphonate were evaluated as inhibitors of a polytopic PGT (WecA from Thermotoga maritima) and a monotopic PGT (PglC from Campylobacter jejuni). Although CHF-BP most closely mimics diphosphate with respect to its acid/base properties, the less basic CF2-BP conjugate more strongly inhibited PglC, whereas the more basic CH2-BP analogue was the strongest inhibitor of WecA. These surprising differences indicate different modes of ligand binding for the different PGT superfamilies, implicating a modified P-O- interaction with the structural Mg2+. For the monoPGT enzyme, the two diastereomeric CHF-BP conjugates, which feature a chiral center at the Pα-CHF-Pß carbon, also exhibited strikingly different binding affinities and the inclusion of GlcNAc with the native α-anomer configuration significantly improved binding affinity. UBP-sugars are thus revealed as informative new mechanistic probes of PGTs that may aid development of novel antibiotic agents for the exclusively prokaryotic monoPGT superfamily.

Uridine Bisphosphonates Differentiate Phosphoglycosyl Transferase Superfamilies.

Complex bacterial glycoconjugates are essential for bacterial survival, and drive interactions between pathogens and symbionts, and their human hosts. Glycoconjugate biosynthesis is initiated at the membrane interface by phosphoglycosyl transferases (PGTs), which catalyze the transfer of a phosphosugar from a soluble uridine diphospho-sugar (UDP-sugar) substrate to a membrane-bound polyprenol-phosphate (Pren-P). Two distinct superfamilies of PGT enzymes, denoted as polytopic and monotopic, carry out this reaction but show striking differences in structure and mechanism. With the goal of creating non-hydrolyzable mimics (UBP-sugars) of the UDP-sugar substrates as chemical probes to interrogate critical aspects of these essential enzymes, we designed and synthesized a series of uridine bisphosphonates (UBPs), wherein the diphosphate bridging oxygen of the UDP and UDP-sugar is replaced by a substituted methylene group (CXY; X/Y = F/F, Cl/Cl, (S)-H/F, (R)-H/F, H/H, CH3/CH3). These compounds, which incorporated as the conjugating sugar an N-acetylglucosamine (GlcNAc) substituent at the ß-phosphonate, were evaluated as inhibitors of a representative polytopic PGT (WecA from Thermotoga maritima) and a monotopic PGT (PglC from Campylobacter jejuni). Although CHF-BP most closely mimics pyrophosphate with respect to its acid/base properties, the less basic CF2-BP conjugate most strongly inhibited PglC, whereas the more basic CH2-BP analogue was the strongest inhibitor of WecA. These surprising differences indicate different modes of ligand binding for the different PGT superfamilies implicating a modified P-O- interaction with the structural Mg2+, consistent with their catalytic divergence. Furthermore, at least for the monoPGT superfamily example, this was not the sole determinant of ligand binding: the two diastereomeric CHF-BP conjugates, which feature a chiral center at the Pα-CHF-Pß carbon, exhibited strikingly different binding affinities and the inclusion of GlcNAc with the native α-anomer configuration significantly improved binding affinity. UBP-sugars are a valuable tool for elucidating the structures and mechanisms of the distinct PGT superfamilies and offer a promising scaffold to develop novel antibiotic agents for the exclusively prokaryotic monoPGT superfamily.

Small molecule targeting of transcription-replication conflict for selective chemotherapy.

Targeting transcription replication conflicts, a major source of endogenous DNA double-stranded breaks and genomic instability could have important anticancer therapeutic implications. Proliferating cell nuclear antigen (PCNA) is critical to DNA replication and repair processes. Through a rational drug design approach, we identified a small molecule PCNA inhibitor, AOH1996, which selectively kills cancer cells. AOH1996 enhances the interaction between PCNA and the largest subunit of RNA polymerase II, RPB1, and dissociates PCNA from actively transcribed chromatin regions, while inducing DNA double-stranded breaks in a transcription-dependent manner. Attenuation of RPB1 interaction with PCNA, by a point mutation in RPB1's PCNA-binding region, confers resistance to AOH1996. Orally administrable and metabolically stable, AOH1996 suppresses tumor growth as a monotherapy or as a combination treatment but causes no discernable side effects. Inhibitors of transcription replication conflict resolution may provide a new and unique therapeutic avenue for exploiting this cancer-selective vulnerability.

Novel Peptide Therapeutic Approaches for Cancer Treatment.

Peptides are increasingly being developed for use as therapeutics to treat many ailments, including cancer. Therapeutic peptides have the advantages of target specificity and low toxicity. The anticancer effects of a peptide can be the direct result of the peptide binding its intended target, or the peptide may be conjugated to a chemotherapy drug or radionuclide and used to target the agent to cancer cells. Peptides can be targeted to proteins on the cell surface, where the peptide-protein interaction can initiate internalization of the complex, or the peptide can be designed to directly cross the cell membrane. Peptides can induce cell death by numerous mechanisms including membrane disruption and subsequent necrosis, apoptosis, tumor angiogenesis inhibition, immune regulation, disruption of cell signaling pathways, cell cycle regulation, DNA repair pathways, or cell death pathways. Although using peptides as therapeutics has many advantages, peptides have the disadvantage of being easily degraded by proteases once administered and, depending on the mode of administration, often have difficulty being adsorbed into the blood stream. In this review, we discuss strategies recently developed to overcome these obstacles of peptide delivery and bioavailability. In addition, we present many examples of peptides developed to fight cancer.

Synthesis of 8-oxo-dGTP and its ß,γ-CH2-, ß, γ-CHF-, and ß, γ-CF2- analogues.

Three novel 8-oxo-dGTP bisphosphonate analogues of 3 in which the bridging ß,γ-oxygen is replaced by a methylene, fluoromethylene or difluoromethylene group (4-6, respectively) have been synthesized from 8-oxo-dGMP 2 by reaction of its morpholine 5'-phosphoramidate 14 or preferably, its N-methylimidazole 5'-phosphoramidate 15 with n-tributylammonium salts of the appropriate bisphosphonic acids, 11-13. The latter method also provides a convenient new route to 3. Analogues 4-6 may be useful as mechanistic probes for the role of 3 in abnormal DNA replication and repair.

Kinetic Effects of ß,γ-Modified Deoxynucleoside 5'-Triphosphate Analogues on RNA-Catalyzed Polymerization of DNA.

A recently described DNA polymerase ribozyme, obtained by in vitro evolution, provides the opportunity to investigate mechanistic features of RNA catalysis using methods that previously had only been applied to DNA polymerase proteins. Insight can be gained into the transition state of the DNA polymerization reaction by studying the behavior of various ß,γ-bridging substituted methylene (CXY; X, Y = H, halo, methyl) or imido (NH) dNTP analogues that differ with regard to the pKa4 of the bisphosphonate or imidodiphosphate leaving group. The apparent rate constant (kpol) of the polymerase ribozyme was determined for analogues of dGTP and dCTP that span a broad range of acidities for the leaving group, ranging from 7.8 for the CF2-bisphosphonate to 11.6 for the CHCH3-bisphosphonate. A Brønsted plot of log(kpol) versus pKa4 of the leaving group demonstrates linear free energy relationships (LFERs) for dihalo-, monohalo-, and non-halogen-substituted analogues of the dNTPs, with negative slopes, as has been observed for DNA polymerase proteins. The unsubstituted dNTPs have a faster catalytic rate than would be predicted from consideration of the linear free energy relationship alone, presumably due to a relatively more favorable interaction of the ß,γ-bridging oxygen within the active site. Although the DNA polymerase ribozyme is considerably slower than DNA polymerase proteins, it exhibits a similar LFER fingerprint, suggesting mechanistic commonality pertaining to the buildup of negative charge in the transition state, despite the very different chemical compositions of the two catalysts.

Involvement of TGF-ß and Autophagy Pathways in Pathogenesis of Diabetes: A Comprehensive Review on Biological and Pharmacological Insights.

Despite recent advancements in clinical drugs, diabetes treatment still needs further progress. As such, ongoing research has attempted to determine the precise molecular mechanisms of the disorder. Specifically, evidence supports that several signaling pathways play pivotal roles in the development of diabetes. However, the exact molecular mechanisms of diabetes still need to be explored. This study examines exciting new hallmarks for the strict involvement of autophagy and TGF-ß signaling pathways in the pathogenesis of diabetes and the design of novel therapeutic strategies. Dysregulated autophagy in pancreatic ß cells due to hyperglycemia, oxidative stress, and inflammation is associated with diabetes and accompanied by dysregulated autophagy in insulin target tissues and the progression of diabetic complications. Consequently, several therapeutic agents such as adiponectin, ezetimibe, GABA tea, geniposide, liraglutide, guava extract, and vitamin D were shown to inhibit diabetes and its complications through modulation of the autophagy pathway. Another pathway, TGF-ß signaling pathway, appears to play a part in the progression of diabetes, insulin resistance, and autoimmunity in both type 1 and 2 diabetes and complications in diabetes. Subsequently, drugs that target TGF-ß signaling, especially naturally derived ones such as resveratrol, puerarin, curcumin, hesperidin, and silymarin, as well as Propolis, Lycopus lucidus, and Momordica charantia extracts, may become promising alternatives to current drugs in diabetes treatment. This review provides keen insights into novel therapeutic strategies for the medical care of diabetes.

Completing the ß,γ-CXY-dNTP Stereochemical Probe Toolkit: Synthetic Access to the dCTP Diastereomers and 31P and 19F NMR Correlations with Absolute Configurations.

Nucleoside 5'-triphosphate (dNTP) analogues in which the ß,γ-oxygen is mimicked by a CXY group (ß,γ-CXY-dNTPs) have provided information about DNA polymerase catalysis and fidelity. Definition of CXY stereochemistry is important to elucidate precise binding modes. We previously reported the (R)- and (S)-ß,γ-CHX-dGTP diastereomers (X = F, Cl), prepared via P,C-dimorpholinamide CHCl (6a, 6b) and CHF (7a, 7b) bisphosphonates (BPs) equipped with an (R)-mandelic acid as a chiral auxiliary, with final deprotection using H2/Pd. This method also affords the ß,γ-CHCl-dTTP (11a, 11b), ß,γ-CHF (12a, 12b), and ß,γ-CHCl (13a, 13b) dATP diastereomers as documented here, but the reductive deprotection step is not compatible with dCTP or the bromo substituent in ß,γ-CHBr-dNTP analogues. To complete assembly of the toolkit, we describe an alternative synthetic strategy featuring ethylbenzylamine or phenylglycine-derived chiral BP synthons incorporating a photolabile protecting group. After acid-catalyzed removal of the (R)-(+)-α-ethylbenzylamine auxiliary, coupling with activated dCMP and photochemical deprotection, the individual diastereomers of ß,γ-CHBr- (33a, 33b), ß,γ-CHCl- (34a, 34b), ß,γ-CHF-dCTP (35a, 35b) were obtained. The ß,γ-CH(CH3)-dATPs (44a, 44b) were obtained using a methyl (R)-(-)-phenylglycinate auxiliary. 31P and 19F NMR Δδ values are correlated with CXY stereochemistry and pKa2-4 values for 13 CXY-bisphosphonic acids and imidodiphosphonic acid are tabulated.

A pre-catalytic non-covalent step governs DNA polymerase ß fidelity.

DNA polymerase ß (pol ß) selects the correct deoxyribonucleoside triphosphate for incorporation into the DNA polymer. Mistakes made by pol ß lead to mutations, some of which occur within specific sequence contexts to generate mutation hotspots. The adenomatous polyposis coli (APC) gene is mutated within specific sequence contexts in colorectal carcinomas but the underlying mechanism is not fully understood. In previous work, we demonstrated that a somatic colon cancer variant of pol ß, K289M, misincorporates deoxynucleotides at significantly increased frequencies over wild-type pol ß within a mutation hotspot that is present several times within the APC gene. Kinetic studies provide evidence that the rate-determining step of pol ß catalysis is phosphodiester bond formation and suggest that substrate selection is governed at this step. Remarkably, we show that, unlike WT, a pre-catalytic step in the K289M pol ß kinetic pathway becomes slower than phosphodiester bond formation with the APC DNA sequence but not with a different DNA substrate. Based on our studies, we propose that pre-catalytic conformational changes are of critical importance for DNA polymerase fidelity within specific DNA sequence contexts.

Molecular Mechanisms Underlying Cancer Preventive and Therapeutic Potential of Algal Polysaccharides.

BACKGROUND: Algal polysaccharide and oligosaccharide derivatives have been shown to possess a variety of therapeutic potentials and drug delivery applications. Algal polysaccharides contain sulfated sugar monomers derived from seaweed including brown, red, and green microalgae. Here, in this review, the recent progress of algal polysaccharides' therapeutic applications as anticancer agents, as well as underlying cellular and molecular mechanisms was investigated. Moreover, recent progress in the structural chemistry of important polysaccharides with anticancer activities were illustrated. METHODS: Electronic databases including "Scopus", "PubMed", and "Cochrane library" were searched using the keywords "cancer", or "tumor", or "malignancy" in title/abstract, along with "algae", or "algal" in the whole text until July 2018. Only English language papers were included. RESULTS: The most common polysaccharides involved in cancer management were sulfated polysaccharides, Fucoidans, Carageenans, and Ulvan from different species of algae that have been recognized in vitro and in vivo. The underlying anticancer mechanisms of algal polysaccharides included induction of apoptosis, cell cycle arrest, modulation of transduction signaling pathways, suppression of migration and angiogenesis, as well as activation of immune responses and antioxidant system. VEGF/VEGFR2, TGFR/Smad/Snail, TLR4/ROS/ER, CXCL12/ CXCR4, TGFR/Smad7/Smurf2, PI3K/AKT/mTOR, PBK/TOPK, and ß-catenin/Wnt are among the main cellular signaling pathways which have a key role in the preventive and therapeutic effects of algal polysaccharides against oncogenesis. CONCLUSION: Algal polysaccharides play a crucial role in the management of cancer and may be considered the next frontier in pharmaceutical research. Further well-designed clinical trials are mandatory to evaluate the efficacy and safety of algal polysaccharides in patients with cancer.

Targeting AMPK signaling pathway by natural products for treatment of diabetes mellitus and its complications.

Diabetes affects a large population of the world. Lifestyle, obesity, dietary habits, and genetic factors contribute to this metabolic disease. A target pathway to control diabetes is the 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. AMPK is a heterotrimeric protein with α, ß, and γ subunits. In several studies, AMPK activation enhanced glucose uptake into cells and inhibited intracellular glucose production. Impairment of AMPK activity is present in diabetes, according to some studies. Drugs used in the treatment of diabetes, such as metformin, are also known to act through regulation of AMPK. Thus, drugs that activate and regulate AMPK are potential candidates for the treatment of diabetes. In addition, many patients encounter important adverse effects, like hypoglycemia, while using allopathic drugs. As a result, the investigation of plant-derived natural drugs that lack adverse side effects and treat diabetes is necessary. Natural products like berberine, quercetin, resveratrol, and so forth have shown significant potential in regulating and activating the AMPK pathway which can lead to manage diabetes mellitus and its complications.

A Transition-State Perspective on Y-Family DNA Polymerase η Fidelity in Comparison with X-Family DNA Polymerases λ and ß.

Deoxynucleotide misincorporation efficiencies can span a wide 104-fold range, from ∼10-2 to ∼10-6, depending principally on polymerase (pol) identity and DNA sequence context. We have addressed DNA pol fidelity mechanisms from a transition-state (TS) perspective using our "tool-kit" of dATP- and dGTP-ß,γ substrate analogues in which the pyrophosphate leaving group (p Ka4 = 8.9) has been replaced by a series of bisphosphonates covering a broad acidity range spanning p Ka4 values from 7.8 (CF2) to 12.3 [C(CH3)2]. Here, we have used a linear free energy relationship (LFER) analysis, in the form of a Brønsted plot of log( kpol) versus p Ka4, for Y-family error-prone pol η and X-family pols λ and ß to determine the extent to which different electrostatic active site environments alter kpol values. The apparent chemical rate constant ( kpol) is the rate-determining step for the three pols. The pols each exhibit a distinct catalytic signature that differs for formation of right (A·T) and wrong (G·T) incorporations observed as changes in slopes and displacements of the Brønsted lines, in relation to a reference LFER. Common to this signature among all three pols is a split linear pattern in which the analogues containing two halogens show kpol values that are systematically lower than would be predicted from their p Ka4 values measured in aqueous solution. We discuss how metal ions and active site amino acids are responsible for causing "effective" p Ka4 values that differ for dihalo and non-dihalo substrates as well as for individual R and S stereoisomers for CHF and CHCl.

New Chirally Modified Bisphosphonates for Synthesis of Individual Beta,Gamma-CHX-Deoxynucleotide Diastereomers.

Individual diastereomers of CXY bisphosphonate analogues of dNTPs or NTPs are useful chemical stereoprobes to investigate interactions within the chiral active site environment of enzymes such as polymerases and kinases. We previously reported synthetic access to ß,γ-CHX-dGTPs (X = F or Cl) via a bisphosphonate synthon with an (R)-methyl mandelate auxiliary and have extended this approach to dTTP and dATP analogues. As removal of the chiral auxiliary by (Pd/C) hydrogenolysis is incompatible with the cytosine heterocycle and also with X = Br, we have now designed bisphosphonate synthons using (R)-(+)-α-ethylbenzylamine or methyl (R)-(-)-phenylglycine auxiliaries and equipped with an o-nitrobenzyl ester protecting group allowing photochemical deprotection. These new synthons have made possible the first syntheses of individual dCTP and monobromo-substituted dNTP ß,γ-CHX diastereomers.

Anthocyanins in the Management of Metabolic Syndrome: A Pharmacological and Biopharmaceutical Review.

The term "metabolic syndrome" (MetS) refers to a combination of diabetes, high blood pressure, and obesity. The origin of MetS includes a combination of multiple factors, such as sedentary lifestyle, unhealthy diet choice, and genetic factors. MetS is highly prevalent and adversely affects the general population by elevating risk of cardiovascular complications, organ failure, and much other pathology associated with late-stage diabetes. Anthocyanins (ANTs) are health-promoting bioactive compounds belonging to the flavonoids subclass of polyphenols. Numerous studies have reported the potential therapeutic benefits on MetS syndrome and diabetes from fruits rich in ANTs. This review summarizes the role of several dietary ANTs on preventing and managing MetS as well as the pharmacological mechanisms and biopharmaceutical features of their action. We also discuss potential nanoformulation and encapsulation approaches that may enhance the bioefficacy of ANTs in MetS. Experiments have demonstrated that ANTs may attenuate the symptoms of MetS via improving insulin resistance, impaired glucose tolerance, dyslipidaemia, cholesterol levels, hypertension, blood glucose, protecting ß cells, and preventing free radical production. In brief, the intake of ANT-rich supplements should be considered due to their plausible ability for prevention and management of MetS. Additionally, randomized double-blind clinical trials are obligatory for evaluating the bioefficacy and pharmacological mechanisms of ANTs and their pharmaceutical formulations in patients with MetS.

Correction to: A systematic review of nano formulation of natural products for the treatment of inflammatory bowel disease: drug delivery and pharmacological targets.

The corresponding author, Mohammad Hosein Farzaei, affiliation is Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. The correct spelling of the 7th author surname is Iranpanah.

A systematic review of nano formulation of natural products for the treatment of inflammatory bowel disease: drug delivery and pharmacological targets.

Inflammatory bowel diseases (IBD), which is classified into Crohn's disease and ulcerative colitis, are among chronic gastrointestinal diseases with unknown pathogenesis. Diverse strategies have been applied for the treatment of this chronic disease. However, selective and site-specific routes of drug delivery to the inflamed location of the colon remain of high importance. Consequently, the application and effects of natural products in the form of nanoformulation and stimuli responsive nanoparticles as a novel strategy for the treatment of IBD are discussed in this review article. This approach may potentially overcome some complications that are associated with conventional means of colon drug delivery. Meanwhile, in vitro and in vivo studies pave the way for understanding of the mechanism that lies behind this chronic relapsing disease and potentially more effective treatment. Graphical abstract ᅟ.

Probing DNA Base-Dependent Leaving Group Kinetic Effects on the DNA Polymerase Transition State.

We examine the DNA polymerase ß (pol ß) transition state (TS) from a leaving group pre-steady-state kinetics perspective by measuring the rate of incorporation of dNTPs and corresponding novel ß,γ-CXY-dNTP analogues, including individual ß,γ-CHF and -CHCl diastereomers with defined stereochemistry at the bridging carbon, during the formation of right (R) and wrong (W) base pairs. Brønsted plots of log kpol versus p Ka4 of the leaving group bisphosphonic acids are used to interrogate the effects of the base identity, the dNTP analogue leaving group basicity, and the precise configuration of the C-X atom in R and S stereoisomers on the rate-determining step ( kpol). The dNTP analogues provide a range of leaving group basicity and steric properties by virtue of monohalogen, dihalogen, or methyl substitution at the carbon atom bridging the ß,γ-bisphosphonate that mimics the natural pyrophosphate leaving group in dNTPs. Brønsted plot relationships with negative slopes are revealed by the data, as was found for the dGTP and dTTP analogues, consistent with a bond-breaking component to the TS energy. However, greater multiplicity was shown in the linear free energy relationship, revealing an unexpected dependence on the nucleotide base for both A and C. Strong base-dependent perturbations that modulate TS relative to ground-state energies are likely to arise from electrostatic effects on catalysis in the pol active site. Deviations from a uniform linear Brønsted plot relationship are discussed in terms of insights gained from structural features of the prechemistry DNA polymerase active site.

Ultrasound-electrospinning-assisted fabrication and sensing evaluation of a novel membrane as ultrasensitive sensor for copper (II) ions detection in aqueous environment.

The present study has reported an optimized fabrication and application of a novel PVA/TEOS/Schiff base nanofibers membrane as a highly sensitive copper (II) ions in aqueous environment. Here in, for first time, an ultrasound-assisted synthesized symmetric Schiff base has been immobilized on a hybrid polyvinyl alcohol (PVA) and TEOS using electrospinning technique for detection and filtration of copper ions. For this purpose, various working parameters were evaluated and finally the optimized nano fibers membrane was synthesized with 72 nm thickness and PVA/TEOS/Schiff base ratio of (wt%) 8:6:1. The optimized sample named PTLNFM has been employed successfully as an ultra sensitive chemosensor for Cu (II) detection in real samples. The immobilized Schiff base used as a chelating agent could detect copper (II) in the range from 9.34 × 10-8 to 1.15 × 10-5 mol L-1 with the following correlation equation: Absorbance = 0.066 [Cu2+] × 10-6 + 0.095 and R2 = 0.992 and LOD of 1.27 × 10-8 mol L-1 which was lower than most of the reported detection limits in the previous literatures. Validity of this method has been carried out by analysis of Cu2+ in real samples with satisfying recoveries of over 96.11-99.24%.The developed membrane could be offered for diverse use such as medical or industrial applications.

A novel high performance nano chemosensor for copper (II) ion based on an ultrasound-assisted synthesized diphenylamine-based Schiff base: Design, fabrication and density functional theory calculations.

A novel high selective colorimetric chemosensor was introduced based on a nano diphenyl-based Schiff base (H2L), 2,2'-((1E,1'E)-(((hexylazanediyl)bis(4,1-phenylene))bis(methanylylidene))bis(azanylylidene))bis(4-methylphenol) that synthesized using sonochemical method. H2L was characterized by FT-IR, MS, TGA, 1H NMR, 13C NMR, SEM and elemental analysis techniques, then fabricated as the portable strips for sensing copper (II) ions in aqueous media. The binding interaction between H2L and various metal ions was investigated by UV-Vis spectroscopic that showed favorable coordination toward Cu2+ ion. H2L exhibited binding-induced color changes from yellow to pink and practically no interference in the presence of other metal ions, i.e., Cr2+, Mn2+, Fe2+, Co2+, Ni2+, Zn2+, Cd2+, Hg2+, Pb2+, Mg2+ and Ca2+. The chemsensor showd the color change from yellow to pink in presence of copper (II) ion in aqueous media due to binging of H2L and Cu (II). This sensor can determine the copper (II) at in the rang of 7.5 × 10-8-1.8 × 10-5 mol L-1 with a correlation equation: Absorbance = 0.0450[Cu2+] × 10-6 + 0.71 and R2 = 0.975 and low detection limit of 1.89 × 10-8 mol L-1. Density functional theory (DFT) calculations were carried out at the B3LYP levels of theory with B3LYP/6-311+G(d,p) and LANL2DZ/6-311+G(d,p) basis sets for chemosensor and its copper complex respectively. The optimized geometry, harmonic vibrational frequencies, 1H NMR and 13C NMR chemical, Molecular orbital (M.O.), Mulliken population analysis (MPA), contour of Electrostatic Potential (ESP) and Molecular Electrostatic Potential (MEP) map of H2L were calculated which show good agreement with behavior of sensor for detection of Cu2+ ion.