- Photo-protective effects of selected furocoumarins on β-pinene, R-(+)-limonene and γ-terpinene upon UV-A irradiation
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The effect of furocoumarins on terpene photo-oxidation under UV-A light was investigated. For this purpose, four furocoumarins (8-methoxypsoralen, bergapten, bergaptol, bergamottin) each at a level of 5%, was added to solutions of the terpenes β-pinene, R-(+)-limonene and γ-terpinene in ethanol followed by UV irradiation at 366 nm. Bergaptol and bergamottin were synthesized and fully elucidated by NMR spectroscopy. UV-induced transformation of all terpenes was substantially reduced in the presence of furocoumarins. Best photo-protection was observed for γ-terpinene with the addition of bergaptol, i.e. degradation was reduced by 73% compared to the neat substance over a time period of ten days. Bergamottin (50.2%), bergapten (39.8%) and 8-methoxypsoralen (39.6%) also reduced degradation substantially. The protective effect of bergaptol was even noticeable at low concentrations of 0.1%. The main oxidation product of γ-terpinene was p-cymene. Limonene and β-pinene showed a predominated hydroperoxide formation under UV light which could almost completely prevented in the presence of furocoumarins. The protective effect of furocoumarins was presumably due to energy dissipation as a result of the conversion of high energetic radiation (UV-A) into visible light via fluorescence. Phosphorescence or self-quenching within the triplet state were further mechanisms avoiding reactions of excited furocoumarins with the terpenes under investigation. Hence, the photo-stability of the furocoumarins themselves correlated with the extent of their protective effect on all three terpenes.
- Bitterling, Hannes,Kammerer, Dietmar R.,Lorenz, Peter,Stintzing, Florian C.,Vetter, Walter
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- Parallel evolution of UbiA superfamily proteins into aromatic O-prenyltransferases in plants
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Plants produce ~300 aromatic compounds enzymatically linked to prenyl side chains via C–O bonds. These O-prenylated aromatic compounds have been found in taxonomically distant plant taxa, with some of them being beneficial or detrimental to human health. Although their O-prenyl moieties often play crucial roles in the biological activities of these compounds, no plant gene encoding an aromatic O-prenyltransferase (O-PT) has been isolated to date. This study describes the isolation of an aromatic O-PT gene, CpPT1, belonging to the UbiA superfamily, from grapefruit (Citrus × paradisi, Rutaceae). This gene was shown responsible for the biosynthesis of O-prenylated coumarin derivatives that alter drug pharmacokinetics in the human body. Another coumarin O-PT gene encoding a protein of the same family was identified in Angelica keiskei, an apiaceous medicinal plant containing pharmaceutically active O-prenylated coumarins. Phylogenetic analysis of these O-PTs suggested that aromatic O-prenylation activity evolved independently from the same ancestral gene in these distant plant taxa. These findings shed light on understanding the evolution of plant secondary (specialized) metabolites via the UbiA superfamily.
- Munakata, Ryosuke,Olry, Alexandre,Takemura, Tomoya,Tatsumi, Kanade,Ichino, Takuji,Villard, Cloé,Kageyama, Joji,Kurata, Tetsuya,Nakayasu, Masaru,Jacob, Florence,Koeduka, Takao,Yamamoto, Hirobumi,Moriyoshi, Eiko,Matsukawa, Tetsuya,Grosjean, Jérémy,Krieger, Célia,Sugiyama, Akifumi,Mizutani, Masaharu,Bourgaud, Frédéric,Hehn, Alain,Yazaki, Kazufumi
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- Natural oxyprenylated coumarins are modulators of melanogenesis
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Naturally occurring coumarins 7-isopentenyloxycoumarin, auraptene, and umbelliprenin are able to modulate the biosynthesis of melanin in murine Melan-a cells probably through the interaction with selected biological targets like estrogen receptor β and aryl hydrocarbon receptor. Such a modulation strictly depends on the individual structure of the coumarin: the presence of a 3,3-dimethylallyloxy side chain is a structural determinant for tanning activation whereas a farnesyl one leads to the opposite effect. The parent compound with a free OH group, umbelliferone, did not provide any interaction. Other coumarins assayed, having shorter chains and/or being substituted in other positions, and prenyloxypsoralens, were not active or not further investigated in this context being cytotoxic at low doses.
- Fiorito, Serena,Epifano, Francesco,Preziuso, Francesca,Cacciatore, Ivana,di Stefano, Antonio,Taddeo, Vito Alessandro,de Medina, Philippe,Genovese, Salvatore
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p. 274 - 282
(2018/05/14)
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- Structure-activity relationships for naturally occurring coumarins as β-secretase inhibitor
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The present study was demonstrated to evaluate the effects of naturally occurring coumarins (NOCs) including simple coumarins, furanocoumarins, and pyranocoumarins on the inhibition of β-secretase (BACE1) activity. Of 41 NOCs examined, some furanocoumarins inhibited BACE1 activity, but simple coumarins and pyranocoumarins did not affect. The most potent inhibitor was 5-geranyloxy-8-methoxypsoralen (31), which has an IC50 value of 9.9 μM. Other furanocoumarin derivatives, for example, 8-geranyloxy-5- methoxypsoralen (35), 8-geranyloxypsoralen (24), and bergamottin (18) inhibited BACE1 activity, with the IC50 values 25.0 μM. Analyses of the inhibition mechanism by Dixon plots and Cornish-Bowden plots showed that compounds 18, 31 and 35 were mixed-type inhibitor. The kinetics of inhibition of BACE1 by coumarins 24 was non-competitive inhibitors.
- Marumoto, Shinsuke,Miyazawa, Mitsuo
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supporting information; experimental part
p. 784 - 788
(2012/03/22)
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- Design, synthesis and evaluation of furanocoumarin monomers as inhibitors of CYP3A4
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A number of furanocoumarins isolated from grapefruit juice have been found to inhibit CYP3A4 activity in vitro. In this study, we have designed and synthesised a range of analogues based on bergamottin to investigate the relationship between chemical stru
- Row,Brown,Stachulski,Lennard
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p. 1604 - 1610
(2008/02/03)
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- SYNTHESIS OF SPIRO ORTHO ESTERS, SPIRO ORTHO CARBONATES, AND INTERMEDIATES
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Ortho esters and ortho carbonates can be produced by alkylating esters and carbonates with, for example, the hexafluorophosphate salt of a trialkyl oxonium ion. The spiro species are useful intermediates in the synthesis of complex organic molecules. Synt
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- Synthesis and biological evaluation of 6',7'-dihydroxybergamottin (6,7-DHB, a naturally occurring inhibitor of cytochrome P450 3A4
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The recently isolated inhibitor of cytochrome P450 CYP3A4, 6',7'-dihydroxybergamottin (6,7-DHB), was synthesized by an efficient route that is readily adaptable to the production of analogues. The compound was evaluated as an inhibitor of 3A4 in a purified enzyme preparation, as well as against human liver microsomes and human 3A4 expressed in Escherichia coil membrane. In each case, 6,7-DHB proved to be a potent NADPH- and time dependent inactivator of 3A4.
- Bellevue III, Frank H.,Woster, Patrick M.,Edwards, David J.,He, Kan,Hollenberg, Paul F.
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p. 2593 - 2598
(2007/10/03)
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