COSY catalyses trans-cis isomerization and lactonization in the biosynthesis of coumarins

Coumarins, also known as 1,2-benzopyrones, comprise a large class of secondary metabolites that are ubiquitously found throughout the plant kingdom. In many plant species, coumarins are particularly important for iron acquisition and plant defence. Here, we show that COUMARIN SYNTHASE (COSY) is a key enzyme in the biosynthesis of coumarins. Arabidopsis thaliana cosy mutants have strongly reduced levels of coumarin and accumulate o-hydroxyphenylpropanoids instead. Accordingly, cosymutants have reduced iron content and show growth defects when grown under conditions in which there is a limited availabil-ity of iron. Recombinant COSY is able to produce umbelliferone, esculetin and scopoletin from their respective o-hydroxycin-namoyl-CoA thioesters by two reaction steps—a trans–cis isomerization followed by a lactonization. This conversion happens partially spontaneously and is catalysed by light, which explains why the need for an enzyme for this conversion has been overlooked. The combined results show that COSY has an essential function in the biosynthesis of coumarins in organs that are shielded from light, such as roots. These findings provide routes to improving coumarin production in crops or by microbial fermentation

Time-Dependent Density Functional Theory Investigation of the Ground and Excited States of Coumarins 102, 152, 153, and 343

We present calculations of various properties of the ground and excited electronic states of coumarins 102, 152, 153, and 343. Using density functional theory (DFT) and time-dependent density functional theory (TDDFT), we examine the excitation energies to the S1 and S2 states, the ground and excited-state dipole moments, and the lowest ionization potentials of these coumarins. In the case of C153, we locate two distinct S0 minima due to differing conformations of the julolidyl ring structure and compare properties for the syn and anti conformers. For C343, we examine the possibility of proton transfers in the ground and S1 states of the system. We find that (1) DFT tends to overestimate the ground-state dipole moments in these systems, (2) excellent agreement is obtained between TDDFT and experimental vertical excitation energies, (3) TDDFT and CIS yield similar estimates of the dipole moment change between the S0 and S1 states, both of which are in the range of previous experimental estimates, (4) in each case, the S2 state is at least 0.5 eV above the S1 state for the ground-state geometry, and (5) proton transfer is not likely in the ground state of C343 but is only 0.18 eV higher in energy in the S1 state. We also compare the DFT/TDDFT results with RHF/CIS, MP2, and INDO S/CI results. We find good agreement between MP2 and experimental ground-state dipole moments and good agreement between INDO S/CI and TDDFT gas-phase excitation energies

Synthesis of New Iminocoumarins Bearing Parabanic Moieties

The synthesis of novel substituted 3-p-nitro-phenyliminocoumarins and corresponding N-ureaiminocoumarins is described. The condensation of these materials with oxalyl chloride leads to the corresponding N-parabanic iminocoumarins, which have not previously been described, in moderate or good yields and high selectivity. The structures were characterized by Fourier transform infrared, 1H and 13C NMR, and elemental analysis

Lanthanide(III) complexes are more active inhibitors of the Fenton reaction than pure ligands

OBJECTIVES: This study is an extension to our finding of direct anti-oxidant activities of lanthanide(III) complexes with the heterocyclic compound, 5-aminoorotic acid (AOA). In this experiment, we used AOA and coumarin-3-carboxylic acid as the two heterocyclic compounds with anti-oxidant potential, to produce the complexes with different lanthanides. METHODS: Lanthanide(III) complexes were tested on the iron-driven Fenton reaction. The product of this reaction, the hydroxyl radical, was detected by HPLC. RESULTS: All complexes as well as their ligands had positive or neutral effect on the Fenton reaction but their behavior was different. Both pure ligands in low concentration ratio to iron were inefficient in contrast to some of their complexes. Complexes of neodymium, samarium, gadolinium, and partly of cerium blocked the Fenton reaction at very low ratios (in relation to iron) but the effect disappeared at higher ratios. In contrast, lanthanum complexes appeared to be the most promising. Both blocked the Fenton reaction in a dose-dependent manner. CONCLUSION: Lanthanide(III) complexes were proven to block the iron-driven production of the hydroxyl radical. Second, the lanthanide(III) element appears to be crucial for the anti-oxidant effect. Overall, lanthanum complexes may be promising direct anti-oxidants for future testing

Characterization of Dimethylsulfoxide / Glycerol Mixtures: A Binary Solvent System for the Study of "Friction-Dependent" Chemical Reactivity

The properties of binary mixtures of dimethylsulfoxide and glycerol, measured by several techniques, are reported. Special attention is given to those properties contributing or affecting chemical reactions. In this respect the investigated mixture behaves as a relatively simple solvent and it is especially well suited for studies on the influence of viscosity in chemical reactivity. This is due to the relative invariance of the dielectric properties of the mixture. However, special caution must be taken with specific solvation, as the hydrogen-bonding properties of the solvent changes with the molar fraction of glycerol.Comment: 49 pages including appendix, 20 figures and 89 reference

Down-regulatory mechanism of mammea E/BB from Mammea siamensis seed extract on Wilms' Tumor 1 expression in K562 cells.

BackgroundWilms' tumor 1 (WT1) is a biological marker for predicting leukemia progression. In this study, mammea E/BB, an active compound from Saraphi (Mammea siamensis) seed extract was examined for its effect on down-regulatory mechanism of WT1 gene expression, WT1 protein and mRNA stability, and cell proliferation in K562 cell line.MethodsM. siamensis seeds were obtained from the region of Chiang Mai (North of Thailand). Mammea E/BB was extracted from seeds of M. siamensis. WT1 protein expression and stability were evaluated by Western blot analysis. WT1 mRNA stability was assessed by qRT-PCR. WT1-DNA binding and WT1 promoter activity were assayed by ChIP assay and luciferase-reporter assay, respectively. Cell cycle arrest was studied by flow cytometry.ResultsTreatment with mammea E/BB led to down-regulation of WT1 expression. The suppression of WT1 expression did not involve protein and mRNA degradation. Rather, WT1 protein was down-regulated through disruption of transcriptional auto-regulation of the WT1 gene. Mammea E/BB inhibited WT1-DNA binding at the WT1 promoter and decreased luciferase activity. It also disrupted c-Fos/AP-1 binding to the WT1 promoter via ERK1/2 signaling pathway and induced S phase cell cycle arrest in K562 cells.ConclusionMammea E/BB had pleotropic effects on kinase signaling pathways, resulting in inhibition of leukemia cell proliferation

Isolation, spectroscopic characterization, X-ray, theoretical studies as well as in vitro cytotoxicity of Samarcandin

Samarcandin 1, a natural sesquiterpene-coumarin, was isolated as well as elucidated from F. assa-foetida which has significant effect in Iranian traditional medicine because of its medicinal attitudes. The crystal structure of samarcandin was determined by single-crystal X-ray structure analysis. It is orthorhombic, with unit cell parameters a = 10.8204 (5) Å, b = 12.9894 (7) Å, c = 15.2467 (9) Å, V = 2142.9 (2) Å3, space group P212121 and four symmetry equivalent molecules in the unit cell. Samarcandin was isolated in order to study for its theoretical studies as well as its cellular toxicity as anti-cancer drug against two cancerous cells. In comparison with controls, our microscopic and MTT assay data showed that samarcandin suppresses cancer cell proliferation in a dose-dependent manner with IC50 = 11 μM and 13 for AGS and WEHI-164 cell lines, respectively. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) of the structure was computed by three functional methods and 6-311++G∗∗ standard basis set. The optimized molecular geometry and theoretical analysis agree closely to that obtained from the single crystal X-ray crystallography. To sum up, the good correlations between experimental and theoretical studies by UV, NMR, and IR spectra were found. © 2016 Elsevier Inc. All rights reserved

Methyl 2-oxo-2H-chromene-3-carboxylate

The title compound, C11H8O4, features an almost planar molecule (r.m.s. deviation = 0.033 Å for all non-H atoms). In the crystal, the molecules are linked via C-H...O hydrogen bonds, forming two-dimensional networks lying parallel to (1-21)