Search results for "coumarin"

Photoreactivity of Furocoumarins and DNA in PUVA Therapy: Formation of Psoralen−Thymine Adducts

2008

The mechanism of the [2 + 2] cycloaddition photoreaction of psoralen and a DNA nucleobase, thymine, cornerstone of the furocoumarin-based PUVA (psoralen + UVA radiation) phototherapy, has been studied by the quantum-chemical multiconfigurational CASPT2 method. Triplet- and singlet-mediated mono- and diadduct formations have been determined to take place via singlet-triplet crossings and conical intersections, correlated with the initially promoted triplet or singlet states in different possible reactive orientations. Pyroneside monoadducts are suggested to be formed in the triplet manifold of the system, and to be less prone to yield diadducts because of the properties of the monoadduct low…

Development of new Coumarin-based profluorescent substrates for human cytochrome P450 enzymes

2018

Cytochrome P450 (CYP) enzymes constitute an essential xenobiotic metabolizing system that regulates the elimination of lipophilic compounds from the body. Convenient and affordable assays for CYP enzymes are important for assessing these metabolic pathways.In this study, 10 novel profluorescent coumarin derivatives with various substitutions at carbons 3, 6 and 7 were developed. Molecular modeling indicated that 3-phenylcoumarin offers an excellent scaffold for the development of selective substrate compounds for various human CYP forms, as they could be metabolized to fluorescent 7-hydroxycoumarin derivatives. Oxidation of profluorescent coumarin derivatives to fluorescent metabolites by 1…

Caspase-mediated apoptosis in sponges: cloning and function of the phylogenetic oldest apoptotic proteases from Metazoa

2003

AbstractSponges (phylum Porifera) represent the phylogenetically oldest metazoan phylum. These animals have complex cell adhesion and powerful immune systems which allow the formation of a distinct body plan. Consequently, an apoptotic machinery has to be predicted that allows sponges to eliminate unwanted cells accumulating during development. With the marine sponge Geodia cydonium, it is shown that allografts of these animals undergo apoptosis as demonstrated by apoptotic DNA fragmentation. Extracts from allografts contain an enzymic activity characteristic for caspases; as substrate to determine the cleavage activity, Ac-DEVD-AMC was applied. cDNAs encoding predicted caspase-3-related pr…

Suitability ofMMGBSAfor the selection of correct ligand binding modes from docking results

2018

The estimation of the correct binding mode and affinity of a ligand into a target protein using computational methods is challenging. However, docking can introduce poses from which the correct binding mode could be identified using other methods. Here, we analyzed the reliability of binding energy estimation using the molecular mechanics-generalized Born surface area (MMGBSA) method without and with energy minimization to identify the likely ligand binding modes within docking results. MMGBSA workflow (a) outperformed docking in recognizing the correct binding modes of androgen receptor ligands and (b) improved the correlation coefficient of computational and experimental results of rescor…

Ligand Diversity of Human and Chimpanzee CYP3A4: Activation of Human CYP3A4 by Lithocholic Acid Results from Positive SelectionS⃞

2009

For currently unknown reasons, the evolution of CYP3A4 underwent acceleration in the human lineage after the split from chimpanzee. We investigated the significance of this event by comparing Escherichia coli-expressed CYP3A4 from humans, chimpanzee, and their most recent common ancestor. The expression level of chimpanzee CYP3A4 was ∼50% of the human CYP3A4, whereas ancestral CYP3A4 did not express in E. coli. Steady-state kinetic analysis with 7-benzyloxyquinoline, 7-benzyloxy-4-(trifluoromethyl)coumarin (7-BFC), and testosterone showed no significant differences between human and chimpanzee CYP3A4. Upon addition of α-naphthoflavone (25 μM), human CYP3A4 showed a slightly decreased substr…

SYNTHESIS OF PYRROLO[3,2-H]QUINOLINONES WITH GOOD PHOTOCHEMOTHERAPEUTIC ACTIVITY AND NO DNA DAMAGE

2010

In the search for new photochemotherapeutic agents, a series of derivatives of the ring system pyrrolo[3,2-h]quinoline--bioisosters of the angular furocoumarin angelicin--were synthesized through a four-step synthetic approach, in reasonable overall yields. Eight of the synthesized derivatives showed a remarkable phototoxicity against a panel of four human tumor cell lines and a great dose UV-A dependence, reaching IC₅₀ values at submicromolar level. The mode of cellular death photoinduced by pyrrolo[3,2-h]quinolines was evaluated through a series of flow cytometric analysis and other tests were performed to clarify their mechanism of action.

Differential effect of the enantiomers of phenprocoumon and warfarin on the vitamin K1-epoxide/vitamin K1 ratio in rat plasma.

1979

Photochemical and Photobiological Studies of a Furonaphthopyranone as a Benzo-spaced Psoralen Analog in Cell-free and Cellular DNA

1997

Photobiological activities of the benzo-spaced psoralen analog furonaphthopyranone 3 have been investigated in cell-free and cellular DNA. The molecular geometry parameters of 3 suggest that it should not form interstrand crosslinks with DNA. With cell-free DNA no evidence for crosslinking but also not for monoadduct formation was obtained; rather, the unnatural furocoumarin 3 induces oxidative DNA modifications under near-UVA irradiation. The enzymatic assay of the photosensitized damage in cell-free PM2 DNA revealed the significant formation of lesions sensitive to formamidopyrimidine DNA glycosylase (Fpg protein). In the photooxidation of calf thymus DNA by the furonaphthopyranone 3, 0.2…

Solid-Phase Synthesis of Peptide Libraries Combining α-Amino Acids with Inorganic and Organic Chromophores

2009

The synthesis of two series of peptidic chains composed of bis(terpyridine)ruthenium(II) acceptor units and organic chromophores (coumarin, naphthalene, anthracene, fluorene) by stepwise solid-phase peptide synthesis (SPPS) techniques is described. The first series of dyads comprises directly amide linked chromophores, while the second one possesses a glycine spacer between the two chromophores. All dyads were studied by UV/Vis and NMR spectroscopy, steady-state luminescence, luminescence decay and electrochemistry, as well as by DFT calculations. The results of these studies indicate weak electronic coupling of the chromophores in the ground state. Absorption spectra of all dyads are domin…

A coumarin based gold(i)-alkynyl complex: a new class of supramolecular hydrogelators.

2014

A phosphine-gold(I)-alkynyl-coumarin complex, [Au{7-(prop-2-ine-1-yloxy)-1-benzopyran-2-one}(DAPTA)] (1), was synthesized and the formation of long luminescent fibers in solution was characterized via fluorescence microscopy and dynamic light scattering. The fibers presented strong blue and green luminescence, suggesting that the gold(I) in the complex increased intersystem crossing due to the heavy atom effect, resulting in a significant increase in triplet emission. The X-ray structure of the fibers indicates that both aurophilic, π–π interactions and hydrogen bonding contribute to their formation in aqueous solvents.