Search

6,7-Dihydroxycoumarin (6,7-HC) (aesculetin) is a natural and synthetic coumarin derivative of great interest for use by humans due to their potent antioxidant properties. Considering that there are no reports that assess the in vivo genetic toxicity of 6,7-HC, the aim of the present study was to investigate its genotoxic potential in terms of DNA damage in peripheral blood, liver, bone marrow and testicular cells of Swiss albino mice by the comet assay, and its clastogenic/aneugenic potential in bone marrow cells using the micronucleus test. In addition, the ability of 6,7-HC to modulate the genotoxic effects induced by doxorubicin (DXR) was also preliminarily evaluated. Cytotoxicity was assessed by scoring polychromatic (PCE) and normochromatic (NCE) erythrocytes’ ratio. The test compound was administered orally at doses of 25, 50 and 500 mg kg−1 isolated and also simultaneously to DXR (80 mg kg−1). The results showed that 6,7-HC did not induce significant DNA damage in any of the analyzed cells, and also did not show any significant increase in micronucleated PCE at the three tested doses. The PCE/NCE ratio indicated no cytotoxicity. Moreover, the extent of DNA damage induced by DXR decreased significantly only in peripheral blood and testicular cells, and only at the lowest dose of 6,7-HC.

In last few decades, though significant progress has been made in the treatment and control strategies of tubercular infections by introducing new diagnostic and monitoring tools and combination therapy, it still continues to be severe problem. The need of study was only because of there are many drugs in market to treat infection but most of the drugs are showing resistance because of the same it is difficult to treat the infection. In this study we chosen coumarin nucleus for study. Thus with the aim of developing novel molecule with improved potency for treating Mycobacterium tuberculosis H37Rv strain infections and with decreased probability of developing drug resistance. The synthesis of coumarin derivatives, starting from salicyaldehyde and ethyl acetoacetate, by conventional organic reaction and results of investigations of their anti-mycobacterial activity. MICs of the synthesized compounds are compared with existing drugs Cytotoxicity. Many compounds have shown promising activity while some were inactive. It was found that Compound A1, A2, B1, B2, C1, C2 have shown promising anti tubercular activity against std. Streptomycin. [ABSTRACT FROM AUTHOR]

Four new carbazole-based coumarin derivatives comprising a carbazole core and one or two coumarin chromophores, 7-(diethylamino)-3-(4-(9-( p -tolyl)-9 H -carbazol-3-yl)phenyl)coumarin ( Cz-Ph-C ) and 3,3'-((9-( p -tolyl)-9 H -carbazole-3,6-diyl)bis(4,4′-phenyl))bis(7- (diethylamino)coumarin) ( Cz-2(Ph-C) ), 7-(diethylamino)-3-(5-(9-( p -tolyl)-9H-carbazol-3- yl)thiophen-2-yl)coumarin ( Cz-Th-C ) and 3,3'-((9-( p -tolyl)-9 H -carbazole-3,6-diyl)bis(thiophene- 5,2-diyl))bis(7-(diethylamino)coumarin) ( Cz-2(Th-C) ), were successfully synthesized as the emissive materials for organic light-emitting devices. The photophysical, electrochemical properties and thermal stabilities of the compounds were systematically investigated. The results showed that these coumarin-carbazole hybrids exhibited excellent thermal stabilities and high photoluminescence quantum efficiencies in dichloromethane solutions, and they emitted strong green emissions. The vacuum-processed doped devices with a configuration of ITO/TAPC (20 nm)/TBADN: Coumarin-carbazole hybrid (x wt%, 30 nm)/TPBi (50 nm)/Liq (2 nm)/Al (150 nm) was fabricated, in which the devices based on Cz-Ph-C exhibited the best electroluminescence performance with a maximum brightness of 12910 cd/m 2 and a maximum luminous efficiencies of 7.39 cd/A and a maximum external quantum efficiency (EQE) of 3.36%. [ABSTRACT FROM AUTHOR]

Objective: IMM-H004 (7-hydroxy-5-methoxy-4-methyl-3-[4-methylpiperazin-1-yl]-2H-chromen-2-one) is a novel coumarin derivative that showed better effect in improving global cerebral ischemia in rats. However, the effects and mechanisms in focal cerebral ischemia were not clear. Blood-brain barrier (BBB) protection is a vital strategy for the treatment of cerebral ischemia. This study is to investigate whether IMM-H004 improves brain ischemia injury via BBB protection.Methods: Focal brain ischemia model was induced by middle cerebral artery occlusion for 1 hour and reperfusion (MCAO/R) for 24 hours in rats. IMM-H004 (1.5, 3, 6 mg/kg) and edaravone (positive drug, 6 mg/kg) were administered after 5 minutes of occlusion. Neurological score and TTC staining were used to evaluate the effect of IMM-H004. Evans Blue (EB) staining and electron microscopy were used to assess BBB permeability. Western blot, reverse transcription-polymerase chain reaction, and immunohistochemistry were used to detect the expression of BBB structure-related proteins.Results: Compared with the model group, IMM-H004 in the focal brain ischemia model improved neurological function and reduced cerebral infarction size and edema content. IMM-H004 sharply reduced the EB content and alleviated BBB structure. In addition, IMM-H004 increased the level of zonula occludens (ZO-1) and occluding, decreased the level of aquaporin 4 and matrix metalloproteinase 9, either in cortex or in hippocampus. And all of these changed were related to BBB protection.Conclusion: IMM-H004 improved cerebral ischemia injury via BBB protection. For a potential therapy drug of cerebral ischemia, IMM-H004 merits further study. [ABSTRACT FROM AUTHOR]

In this study, the coumarin-derived schiff bases (HL and HL) have been designed and synthesized. Upon the addition of Zn, both of them show significant fluorescence enhancement owing to inhibits PET and ESIPT process respectively. However, the receptor HL response toward Cd, Mg, Ba, Ca besides Zn and exhibits fluorescence enhancement but not enough to detection of the concentration levels of Zn. [ABSTRACT FROM AUTHOR]

The steady-state fluorescence quenching of novel coumarin derivatives; 4-(2, 6-dibromo-4-methyl-phenoxymethyl)-benzo[h]chromen-2-one [DMB] and 6-methoxy-4- p-tolyoxymethyl-chromen-2-one [TMC] has been studied in toluene, benzene, dioxane, acetonitrile and tetrahydrofuran [THF] using aniline as a quencher at room temperature with a view to understanding the role of diffusion in the quenching mechanism. The probability of quenching per encounter ( p) is calculated in all the solvents. Further, an activation energy for quenching ( E ) was estimated using the values of p and the literature values of activation energy for diffusion ( E ). The magnitudes of these parameters indicate that the fluorescence quenching of these molecules by aniline is not solely due to the material diffusion but there is also a contribution of an activation energy. [ABSTRACT FROM AUTHOR]

A novel coumarin derivatives based fluorescent chemosensor CBH was designed and synthesized by Schiff base reaction, which was connected by 7-(N,N-diethylamino) coumarin-3-aldehyde and 3-methyl-2-benzothiazolinone hydrazone through C=N. X-ray single crystal structure analysis indicated that two aromatic groups of the CBH were almost in the same plane. It displayed enhancement of the fluorescent intensity and absorbance when the sensor CBH interacted with Hg 2+ ions. The chemosensor CBH exhibited a good sensitive and selective recognition towards Hg 2+ ions in the presence of other important relevant metal ions. [ABSTRACT FROM AUTHOR]

• Probe LD-HJZ2 with deep-red emission was developed for imaging LDs within a short time via a wash-free procedure. • Probe LD-HJZ2 showed obviously aggregation-induced emission (AIE) behavior. • The photophysical properties of these two probes were systematically investigated combining with theoretical calculation. In this work, we constructed two novel fluorescent probes based on coumarin derivatives for imaging lipid droplets. The photophysical properties indicated that probe LD-HJZ1 exhibited an aggregation-caused quenching (ACQ) feature, while probe LD-HJZ2 showed obviously aggregation-induced emission (AIE) behavior. In addition, the maximum emission wavelength of probe LD-HJZ2 was localized around 687 nm with 90% water content. Cell imaging experiments demonstrated that the fluorescence images of probes LD-HJZ1 and LD-HJZ2 were overlapped well with the commercial lipid droplet dyes. Interestingly, probe LD-HJZ2 was capable of targeting lipid droplets within a short time (< 1 min) with or without wash-free procedure. Furthermore, probe LD-HJZ2 could be used to detect the changes in the number of lipid droplets under starvation conditions and oleic acid stimulation. This work provides a new perspective for the development of fluorescent probes with deep-red emission for targeting lipid droplets. [ABSTRACT FROM AUTHOR]

In the title compound, C17H18ClNO5, which was synthesized by reacting 4-chloro-3-formylcoumarin, acetic acid and tert-butyl isocyanide, the acetamido side chain is convoluted with ring-to-side chain C—C—C—C, C—C—C—N and C—C—N—C torsion angles of −123.30 (14), −135.73 (12) and 176.10 (12)°, respectively. In the crystal, N—H...O and weak C—H...O hydrogen bonds are present, which together with π–π coumarin-ring interactions [ring centroid separations = 3.4582 (8) and 3.6421 (9) Å], give rise to a layered structure lying parallel to (001).

The asymmetric unit of the title compound, C13H14O3, contains two independent molecules, A and B, that are interconnected through an offset π–π interaction [inter-centroid separation = 3.6087 (4) Å]. The fused benzene and pyran-2-one rings in each molecule are essentially coplanar, having dihedral angles of 1.22 (12) and 1.57 (12)° for molecules A and B, respectively. Similarly, the coumarin ring system and the 7-propoxy substituent are close to being coplanar [C—C—O—C torsion angles = 2.9 (2) and 1.4 (2)° for molecules A and B, respectively]. In the crystal, the molecules are connected by C—H...O hydrogen bonds, forming supramolecular tapes along [100] that are linked into a three-dimensional network by C—H...π interactions, as well as by the aforementioned π–π interactions.

Triple negative breast cancer constitutes to about 21.8 percent of the total breast cancer related cases. Its ability to affect young ladies and in pre-menstrual stage makes this a disease of concern worldwide. The current treatment regimens involve chemotherapy which are used for treatment of other cancer types. In this regard, there is a need for specific and targeted drug candidate for its effective treatment. In the current study, assessment of coumarin derivative 2-(2-(6- Methyl-2-Oxo-2H-chromen-4-yl) acetamido)-3-phenylpropanoic acid is carried out both In-silico and In-vitro methods. Frizzled transmembrane proteins of Wingless-related integration site signaling pathway was targeted in which Frizzled-7 proved to a prospective target and showed a binding energy of -6.78 kcal/mol. The complex was subjected to molecular dynamics simulation for 200 ns and showed stable interaction with cysteine rich domain of the receptor. Cell proliferation, viability and apoptosis assay were performed on MDA-MB-231 and MDA-MB-468 cell lines with an IC 50 value of 81.23 and 84.68 µM, respectively. The results provide a drug candidate which is derivative of a natural compound with targeted TNBC inhibitory effect. Communicated by Ramaswamy H. Sarma.

A new coumarin derivative 2-(2-mercaptophenylimino)-4-methyl-2H-chromen-7-ol (COMSB) was synthesized and characterized with the help of 1 H, 13 C NMR, FT-IR, FT-Raman and mass spectrometry. All quantum calculations were performed at DFT level of theory using B3LYP functional and 6-31G (d,p) as basis set. The UV–Vis spectrum studied by TD-DFT theory, with a hybrid exchange-correlation functional using Coulomb-attenuating method (CAM-B3LYP) in solvent phase gives similar pattern of bands, at energies and is consistent with that of experimental findings. The detailed analysis of vibrational (IR and Raman) spectra and their assignments has been done by computing Potential Energy Distribution (PED) using Gar2ped. Intra-molecular interactions were analyzed by ‘Atoms in molecule’ (AIM) approach. Computed first static hyperpolarizability (β 0 = 8.583 × 10 −30 esu) indicates non-linear optical (NLO) response of the molecule. Molecular docking studies show that the title molecule may act as potential acetylcholine esterase (AChE) inhibitor. [ABSTRACT FROM AUTHOR]

Here, we synthesized a new coumarinyl chalcone derivative 3-[ 3-( 3-Methyl-thiophen-2-yl) -acryloyl] -chromen-2-one (MTC) by simple and proficient method. A comprehensive study on the photophysics of a coumarinyl chalcone derivative having pi-conjugated potential chromophore system 3-[ 3-( 3-Methyl-thiophen-2-yl) -acryloyl] -chromen-2-one (MTC) has been carried out spectroscopically. The electronic absorption and emission characteristic of MTC were studied in different protic and aprotic solvents using absorption and steady-state fluorescence techniques. The spectral behavior of this compound is found to be extremely sensitive to the polarity and hydrogen bonding nature of the solvent. The compound shows very strong solvent polarity dependent changes in their photophysical characteristics, namely, remarkable red shift in the emission spectra with increasing solvent polarity, change in Stokes shift, significant reduction in the fluorescence quantum yield; indicating that the fluorescence states of these compounds are of intramolecular charge transfer (ICT) character. The solvent effect on the photophysical parameters such as singlet absorption, molar absorptivity, oscillator strength, dipole moment, fluorescence spectra, and fluorescence quantum yield of the compound has been investigated in detail. The difference between the excited and ground state dipole moments (Δ μ) were estimated from solvatochromic methods using Lippert-Mataga and Reichardt's correlations. The prepared compound was also studied by density functional theory (DFT) and time-dependent density functional theory (TDDFT). The results revealed that it could be easily reproduce by computational means. [ABSTRACT FROM AUTHOR]

The probe CT was synthesized and investigated as a novel label-free chemosensor for Ga 3 + detection in water. Probe CT showed remarkable selectivity and sensitivity for Ga 3 + in Tris–HCl aqueous buffer solution (pH 7.0). The chemosensor responded rapidly to Ga 3 + with a 1:1 stoichiometry. Meanwhile, the unapparent changes of fluorescence lifetime decays suggest the turn-on process of probe CT by Ga 3 + which appears to be a static mechanism. [ABSTRACT FROM AUTHOR]

1. Information about the metabolism of compounds is essential in drug discovery and development, risk assessment of chemicals and further development of predictive methods. 2. In vitroandin silicomethods were applied to evaluate the metabolic and inhibitory properties of 6-methylcoumarin, 7-methylcoumarin and 7-formylcoumarin with human CYP2A6, mouse CYP2A5 and pig CYP2A19. 3. 6-Methylcoumarin was oxidized to fluorescent 7-hydroxy-6-methylcoumarin by CYP2A6 (Km: 0.64–0.91 µM;Vmax: 0.81–0.89 min−1) and by CYP2A5 and CYP2A19. The reaction was almost completely inhibited at 10 µM 7-methylcoumarin in liver microsomes of human and mouse, but in pig only 40% inhibition was obtained with the anti-CYP2A5 antibody or with methoxsalen and pilocarpine. 7-Methylcoumarin was a mechanism-based inhibitor for CYP2A6, but not for the mouse and pig enzymes. 7-Formylcoumarin was a mechanism-based inhibitor for CYP2As of all species. 4. Docking and molecular dynamics simulations of 6-methylcoumarin and 7-methylcoumarin in the active sites of CYP2A6 and CYP2A5 demonstrated a favorable orientation of the 7-position of 6-methylcoumarin towards the heme moiety. Several orientations of 7-methylcoumarin were possible in CYP2A6 and CYP2A5. 5. These results indicate that the active site of CYP2A6 has unique interaction properties for ligands and differs in this respect from CYP2A5 and CYP2A19. [ABSTRACT FROM AUTHOR]

[Display omitted] • A PU- co -HCCA nanoemulsion fluorescent probe toward Hg2+ was prepared. • PU- co -HCCA nanoemulsion shows great quantum yields and ppb-level detection limits. • The modified paper with PU- co -HCCA nanoemulsion has a potential in Hg2+ detection. A novel polyurethane (PU- co -HCCA) nanoemulsion bearing coumarin derivative (HCCA) was synthesized as a "turn-on" fluorescent probe and used to modify filter paper, and its sensing properties were investigated. Results showed that PU- co -HCCA nanoemulsion exhibited high selectivity and excellent sensitivity toward Hg2+ over other metal ions, and possessed excellent fluorescence quantum yields of 0.976, ppb-levels detection limits of 1.61 ppb and large Stokes shifts of 101 nm. Meanwhile, as an application example of as-prepared PU- co -HCCA nanoemulsion, a Hg2+ test paper was prepared by modifying filter paper with PU- co -HCCA nanoemulsion, and results indicated that the test paper is portable and convenient and has a wide working pH range. We believe that the PU- co -HCCA nanoemulsion and the modified filter paper can provide a new design principle for the application of fluorescence sensors for metal ions including Hg2+. [ABSTRACT FROM AUTHOR]

• Unique crystal packing with 3D-π-stacking interaction. • Coumarin based novel chemo-sensor for detection of aqueous Co2+, Ni2+ and Cu2+ ions through naked eyes and fluorimetrically. • Interaction with calf-thymus DNA. A new coumarin derivative, 4-amino-3-nitroso-2 H -chromen-2-one (B) was synthesized through a very easy procedure and charecterized by 1H- and 13C- NMR, FTIR, HRMS and single crystal XRD analysis. Its photo-physical characteristics along with its transition metal ion-sensing capability were cultivated. Unique crystal packing with 3D-π-stacking interaction was observed. DFT calculation gave more insight into the electronic properties of B and was found to be in very good agreement with the X-ray data. The studies of solvatochromism of B in various solvents of different polarities as well as its pH dependency have been provided. The compound was employed as a simple fluorimetric as well as colorimetric chemosensor for the investigation of Ni2+, Co2+ and Cu2+ ions. The Job's plot experiments disclosed 2:1, 3:1 and 1:1 stoichiometric bindings between B and the corresponding analyte ions Ni2+, Co2+ and Cu2+, respectively. The detection limits and the binding constant values of B for the Ni2+, Co2+ and Cu2+ions have also been provided. In addition, several experiments employing this chemosensor with calf-thymus DNA (CT-DNA) unveiled itself as a groove binder. A coumarin derivative B with unique crystal packing having 3D-π-stacking interaction, senses aqueous Co2+, Ni2+ and Cu2+ ions, and interacts with CT-DNA through groove binding. DFT calculation gave more insight into the electronic properties of B. The photo-physical studies like solvatochromism of B in various solvents with different polarities, pH dependency of B gave interesting observations. [Display omitted] [ABSTRACT FROM AUTHOR]

Osteoporosis is treated with oral and parenteral bone resorption inhibitors such as bisphosphonates, and parenteral osteogenic drugs including parathyroid hormone (PTH) analogues and anti-sclerostin antibodies. In the present study, we synthesized KY-054, a 4,6-substituted coumarin derivative, and found that it potently promoted osteoblast differentiation with an increase in alkaline phosphatase (ALP) activity at 0.01-1 µM in mouse-derived mesenchymal stem cells (ST2 cells) and rat bone marrow-derived mesenchymal stem cells (BMSCs). In the ovariectomized (OVX) rats, KY-054 (10 mg/kg/d, 8 weeks) increased plasma bone-type ALP activity, suggesting in vivo promoting effects on osteoblast differentiation and/or activation. In dual-energy X-ray absorption (DEXA) scanning, KY-054 significantly increased the distal and diaphyseal femurs areal bone mineral density (aBMD) that was decreased by ovariectomy, indicating its beneficial effects on bone mineral contents (BMC) and/or bone volume (BV). In micro-computed tomography (micro-CT) scanning, KY-054 had no effect on metaphysis trabecular bone loss and microarchitecture parameters weakened by ovariectomy, but instead increased metaphysis and diaphysis cortical bone volume (Ct.BV) and cortical BMC (Ct.BMC) without reducing medullary volume (Med.V), resulting in increased bone strength parameters. It is concluded that KY-054 preferentially promotes metaphysis and diaphysis cortical bone osteogenesis with little effect on metaphysis trabecular bone resorption, and is a potential orally active osteogenic anti-osteoporosis drug candidate.

Two new anthracen- and pyrene-based coumarin derivatives, 3-(4-(anthracen-10-yl)phenyl)coumarin ( 4 ) and 3-(4-(pyrene-1-yl)phenyl)coumarin ( 5 ), were synthesized and characterized by FT-IR, 1 H NMR, element analysis and single crystal X-ray crystallography. The UV–vis absorption and photoluminescence spectra of these coumarin derivatives were investigated. The results show that compound 4 and 5 exhibit blue and blue-green emissions, respectively, under ultraviolet light excitation. Compared with the compound 4 , the emission peak of compound 5 was bathochromically shifted by about 80 nm due to the more planar structure and larger π-conjugation. [ABSTRACT FROM AUTHOR]

One new coumarin derivative (1) and two known compounds, quercetin (2) and glyceraldehyde (3) have been isolated from the whole plants of Euphorbia wallichii. Their structures were elucidated by means of extensive spectroscopic analysis (NMR and ESI-MS) and by comparison with data reported in the literature. This is the first isolation of dihydrocoumarin (1) from the genus of Euphorbia. [ABSTRACT FROM AUTHOR]

Three new compounds, namely (+)-pranferol ( 1 ), antiarone M ( 2 ), and anticerol A ( 3 ), together with 9 known compounds, were obtained from the bark of Antiaris toxicaria . Their chemical structures were elucidated on the basis of spectroscopic methods including UV, IR, (HR) ESI–MS, 1 H, 13 C NMR, HSQC, 1 H- 1 H COSY, HMBC and X-ray crystallographic technique. The absolute configurations of compounds 1 and 2 were determined by modified mosher method and CD spectrum. [ABSTRACT FROM AUTHOR]

The new Cu(II) complexes with 6-acetyl-7-hydroxy-4-methylcoumarin (HL1) and 8-acetyl-7-hydroxy-4-methylcoumarin (HL2) have been obtained by the electrochemical method. The density functional theory calculations and X-ray absorption spectroscopy techniques have been used to geometrically describe a series of new compounds. The studies have been focused on the coordination mode of the hydroxy ligands to the metallic centre. The complexes, Cu(HL1) 2 and Cu(HL2) 2 ⋅ 0.5H 2 O, have flat square geometry with oxygen atoms in the first coordination sphere. Two bidentate anionic coumarins are bonded to the metal cation via the acetyl and deprotonated hydroxyl O atoms. Biological activity, including microbiological and cytotoxic, has been evaluated and found to be enhanced in comparison with the parent ligands. Moreover, the Cu(II) complex with 8-acetyl-7-hydroxy-4-methylcoumarin shows similar antifungal activity as commercially used fluconazole. [ABSTRACT FROM AUTHOR]

Two new copper(II) (2) and nickel(II) (3) complexes with a new coumarin derivative have been synthesized and structurally characterized. The DNA-binding activities of the two complexes have been investigated by spectrometric titrations, ethidium bromide displacement experiments, CD (circular dichroism) spectral analysis, and viscosity measurements. The results indicate that the two complexes, especially the complex 2, can strongly bind to calf-thymus DNA (CT--DNA). The intrinsic binding constants Kb of the complexes with CT-DNA are 2.99 × 105 and 0.61 × 105 for 2 and 3, respectively. Comparative cytotoxic activities of the two complexes are also determined by MTT assay. The results show that the drugs designed here have significant cytotoxic activity against the human hepatic (HepG2), human promyelocytic leukemia (HL60), and human prostate (PC3) cell lines. Cell apoptosis was detected by Annexin V/PI flow cytometry, and the results show that the two copper complexes can induce apoptosis of the three human tumor cells. In conclusions, the two complexes show considerable cytotoxic activity against the three human cancer and induce apoptosis of the threes. [ABSTRACT FROM AUTHOR]

Breast cancer, a heterogeneous disease, is among the most frequently diagnosed diseases and is the second leading cause of death due to cancer among women after lung cancer. Phytoactives (plant-based derivatives) and their derivatives are safer than synthetic compounds in combating chemoresistance. In the current work, a template-based design of the coumarin derivative was designed to target the ADP-sugar pyrophosphatase protein. The novel coumarin derivative (2 R )-2-(( S )- sec -butyl)-5-oxo-4-(2-oxochroman-4-yl)-2,5-dihydro-1 H -pyrrol-3-olate was designed. Molecular docking studies provided a docking score of -6.574 kcal/mol and an MM-GBSA value of -29.15 kcal/mol. Molecular dynamics simulation studies were carried out for 500 ns, providing better insights into the interaction. An RMSD change of 2.4 Å proved that there was a stable interaction and that there was no conformational change induced to the receptor. Metadynamics studies were performed to calculate the unbinding energy of the principal compound with NUDT5, which was found to be -75.171 kcal/mol. In vitro validation via a cytotoxicity assay (MTT assay) of the principal compound was carried out with quercetin as a positive control in the MCF7 cell line and with an IC 50 value of 55.57 (+/-) 0.7 μg/mL. This work promoted the research of novel natural derivatives to discover their anticancer activity.

A fluorescent cationic surfactant with a coumarin derivative (Br-Mac-12) has been designed, synthesized and characterized. The critical association concentration (CAC) and critical micelle concentration (CMC) of Br-Mac-12 was 1.0 × 10 −4 and 1.6 × 10 −3 mol/L, respectively. The interaction between Br-Mac-12 and DNA has been investigated using UV–vis and fluorescence spectroscopy as well as gel electrophoresis and atomic force microscopy (AFM). Both linear and plasmid DNA were condensed to nanoparticles by Br-Mac-12 at a concentration of 320 μM with incubation at 37 °C for 4 h. Br-Mac-12 has a more efficient binding capacity with DNA than the corresponding DTAB without the fluorophore. The groove binding between the coumarin derivative and DNA plays an important role in addition to the electrostatic and hydrophobic interaction for effective DNA condensation inductions. In addition, the condensation process was reversible, and the residual fluorescence of Br-Mac-12 upon binding with DNA remains at 37.5% of the initial value. The results suggest that Br-Mac-12 combined with a fluorophore has the potential for applications in tracing membrane transport in gene delivery and transfection due to its excellent fluorescence property and DNA binding affinity. [ABSTRACT FROM AUTHOR]

New biscyanine dye, 4-{2-[4-(dimethylamino)phenyl]ethenyl}-1-{2-[4-(dimethylamino)phenyl]-1-[4-(2-oxo-2 H-chromen-3-yl)benzoyl]ethenyl}pyridinium bromide, has been prepared via condensation of 4-dimethylaminobenzaldehyde with 4-methyl-1-{2-oxo-2-[4-(2-oxo-2 H-chromen-3-yl)phenyl]ethyl}pyridinium bromide. The latter has been synthesized via the Meerwein reaction of coumarin with 4-acetylphenyldiazonium chloride with subsequent bromination and quaternization of the formed α-bromoketone under the action of 4-methylpyridine. Electronic spectra are analyzed, and quantum-chemical simulation of possible isomers of the biscyanine dye has been performed. [ABSTRACT FROM AUTHOR]

The anion recognition ability of a novel azo dye derived from 4-hydroxycuomarin (L) was investigated by experimental (UV-vis, fluorescence and ¹H NMR) and theoretical [(B3LYP/6-31G(d,p)] methods. Among the surveyed anions, the receptor L showed both naked-eye detectable color and spectral changes in the presence of F-, AcO- and H2PO4- due to the formation of hydrogen bonding complexes followed by deprotonation between these anions and L. [ABSTRACT FROM AUTHOR]

Abstract: A new sensor (LWZn) based on 7-diethylaminocoumarin Schiff base was synthesized to detect Zn2+ in the red emission region due to its extended π-conjugation structure and the strong electron-withdrawing capability of nitrile groups. Although LWZn alone has weak fluorescence, its fluorescence intensity shows a 35-fold increase after combining with Zn2+ probably due to the inhibition of the conformational change in the excited state upon complexation with Zn2+. In addition, LWZn shows a good selectivity to Zn2+ over other metal cations, especially Cd2+, which often responds together with Zn2+. [Copyright &y& Elsevier]

Using structure-based virtual screening approach, a coumarin derivative ( 1) was identified as β-glucuronidase inhibitor. A focused library of coumarin derivatives was synthesized by eco-benign version of chemical reaction, and all synthetic compounds were characterized by using spectroscopy. These compounds were found to be inhibitor of β-glucuronidase with IC values in a micromolar range. All synthetic compounds exhibited interesting inhibitory activity against β-glucuronidase, however, their potency varied substantially from IC = 9.9-352.6 µM. Of twenty-one compounds, four exhibited a better inhibitory profile than the initial hit 1. Interestingly, compounds 1e, 1k, 1n and 1p exhibited more potency than the standard inhibitor with IC values 34.2, 21.4, 11.7, and 9.9 µM, respectively. We further studied their dose responses and also checked our results by using detergent Triton ×-100. We found that our results are true and not affected by detergent. [ABSTRACT FROM AUTHOR]

ABSTRACT Based on chelation-enhanced fluorescence, a new fluorescent coumarin derivative probe 3(1-(7-hydroxy-4-methylcoumarin)ethylidene)hydrazinecarbodithioate for Hg2+, Ag+ and Ag nanoparticles is reported. Fluorescent probe acts as a rapid and highly selective 'off-on' fluorescent probe and fluorescence enhancement by factors 5 to12 times was observed upon selective complexation with Hg2+, Ag+ and Ag nanoparticles. The molar ratio plots indicated the formation of 1:1 complexes between Hg2+ and Ag+ with the probe. The linear response range covers a concentration range 0.1 × 10-5-1.9 × 10-5 mol/L, 0.1 × 10-5-2.3 × 10-5 mol/L and 0.146 × 10-12-2.63 × 10-12 mol/L for Hg2+, Ag+ and Ag nanoparticles, respectively. The interference effect of some anions and cations was also tested. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: In this Letter we present a new probe, (E)-7-(diethylamino)-2-oxo-2H-chromene-3-carbaldehyde oxime (JB), which can detect Cu2+ ions in HEPES buffer under physiological conditions. Benesi–Hildebrand and Job plots demonstrate that the stoichiometry of the Cu2+ complex formed is 2:1. Possible interference with other analytes was examined, and the decrease of the fluorescence of JB at 510nm when it reacts with Cu2+ was shown to be highly selective. This probe accumulates in the plasmalemma of human neuroblastoma SH-SY5Y cells. Molecular dynamics (MD) simulations revealed that JB interacts with the lipid bilayer at the level of the glycerol moieties. [Copyright &y& Elsevier]

Abstract: 7-Hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin (IMM-H004) is a novel coumarin derivative synthesized in our laboratory. The purpose of the current study was to determine the neuroprotective effects of IMM-H004 on PC12 cells and its potential mechanism of action. PC12 cells were subject to oxygen and glucose deprivation (OGD) followed by the restoration of oxygen and glucose (R), which mimics ischemia and reperfusion in vivo. Cell viability was determined by MTT assay. DNA fragmentation was analyzed by DNA ladder. ROS and mitochondrial membrane potential were measured by fluorescent microscope and quantified by Image-Pro Express 6.0 software. ATP was measured by luciferin–luciferase assay. The activation of signal-regulated molecules was assessed by the Western blot analysis. OH formation was determined using the Electron Spin Resonance (ESR) trapping technique in combination with 5, 5-dimethyl-1-pyrroline-N-oxide. OGD/R reduced cell viability and induced cell apoptosis, which were both dose-dependently attenuated by IMM-H004. The accumulation of intracellular reactive oxygen species (ROS) and reduced mitochondrial membrane potential observed in PC12 cells treated with OGD/R, which switch on the mitochondrion-dependent apoptotic pathway, were reversed by IMM-H004. ATP production in OGD/R-treated PC12 cells was elevated by IMM-H004, which suggests that it restored the functions of the mitochondria. OGD/R-induced cytochrome c release from the mitochondria reduced the ratio of apoptotic proteins, Bcl-2/Bax, and induced caspase-3 activation and DNA fragmentation. These changes were significantly inhibited by IMM-H004. IMM-H004 also significantly inhibited OH formation, determined by electron spin resonance, which indicates that it is a potent free-radical scavenger. This study has demonstrated that IMM-H004 protects PC12 cells against OGD/R-induced apoptosis, at least in part, by scavenging excessive ROS and inhibiting the mitochondrion-dependent apoptotic pathway. [Copyright &y& Elsevier]

Abstract: Since P-glycoprotein (P-gp) acts as a barrier to intestinal absorption of various drugs, P-gp inhibitors have been studied as oral absorption enhancers of P-gp substrate drugs. Here, we investigated the in vitro and in vivo effects of a novel coumarin derivative (LL-348) for its P-gp inhibitory activity. With LL-348, accumulation of daunomycin (DNM) increased 270% and efflux of DNM decreased 63% compared to that of DNM alone. Paclitaxel (PTX, 25mg/kg) after oral administration with LL-348 (5mg/kg), the optimal dose of LL-348 as an oral absorption enhancer of PTX, improved the relative bioavailability (RB) of PTX to 961%. In a xenograft animal model, PTX (40mg/kg) treated with LL-348 (10mg/kg) significantly increased the efficacy of PTX. The results collectively demonstrate that LL-348 can provide a therapeutic benefit in the oral absorption of P-gp substrate anticancer drugs [Copyright &y& Elsevier]

ABSTRACT 4-Methylesculetin (4-ME) is a synthetic derivative of coumarin that displays a potent reactive oxygen species (ROS) scavenger and metal chelating agent and therefore has been produced to help reduce the risk of human disease. The main objective of this study was to investigate the in vivo genotoxicity of 4-ME and initially to verify its potential antigenotoxicity on doxorubicin (DXR)-induced DNA damage. Different doses of 4-ME (500, 1000 and 2000 mg kg-1 body weight) were administered by gavage only or with a simultaneous intraperitoneal (i.p.) injection of DXR (80 mg kg-1). The following endpoints were analyzed: DNA damage in peripheral blood, liver, bone marrow, brain and testicle cells according to an alkaline (pH > 13) comet assay and micronucleus induction in bone marrow cells. Cytotoxicity was assessed by scoring polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). No differences were observed between the negative control and the groups treated with a 4-ME dose for any of the endpoints analyzed, indicating that it lacks genotoxic and cytotoxic effects. Moreover, 4-ME demonstrated protective effects against DXR-induced DNA damage at all tested doses and in all analyzed cell types, which ranged from 34.1% to 93.3% in the comet assay and 54.4% to 65.9% in the micronucleus test. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]