Disease relevance of Skimmetin

• After 6, 12, or 24 hours, brains were frozen, and infarct size, degree of edema formation, and local brain pH were quantified by standard histology or the umbelliferone technique, respectively [1].
• To gain information about these mechanisms, we studied the effects of coumarin and 7-hydroxycoumarin in the human lung adenocarcinoma cell line A-427 on the inhibition of: (i) cell proliferation; (ii) cell cycle progression; and (iii) expression of cyclins D1, E and A [2].
• Athamantin (an angular furanocoumarin) and umbelliferone (a simple coumarin) showed no phototoxicity, while linear furanocoumarins exhibited phototoxic activity in the following order: psoralen > bergapten > peucedanin > xanthotoxin [3].
• Antitumour activity of coumarin and 7-hydroxycoumarin against 7,12-dimethylbenz[a]anthracene-induced rat mammary carcinomas [4].
• Female SD rats with established 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumours were treated with coumarin (20 mg/kg body weight; six times per week) or its metabolite 7-hydroxycoumarin (20 mg/kg) for 4 weeks [4].

High impact information on Skimmetin

• The His mutant Fv accelerated the hydrolysis of the 7-hydroxycoumarin ester of 5-(2,4-dinitrophenyl)-aminopentanoic acid 90,000-fold compared to the reaction with 4-methyl imidazole at pH 6.8 and had an initial rate that was 45 times as great as that for the wild-type Fv [5].
• The Coh locus has previously been shown to code for a phenobarbital-inducible enzyme, believed to be a cytochrome P-450, which catalyzes the conversion of coumarin to 7-hydroxycoumarin (umbelliferone) [6].
• Plasma and urine 7-hydroxycoumarin and plasma coumarin concentrations were determined by HPLC [7].
• Under varying conditions of MABP and arterial blood gases, grey-level images of the exposed cortex irradiated with ultraviolet light (340 or 370 nm) were digitised (8 bits) at 15-s intervals after the injection of 1-2 ml of saturated umbelliferone solution into the lingual or external carotid artery of anaesthetised cats and rabbits [8].
• Infusion of ethanol (20 mM), a known inhibitor of glycolysis, decreased the stimulation of glycolysis caused by KCN to 20 mumol/g/hr and lowered maximal rates of 7-hydroxycoumarin production to about 6 mumol/g/hr [9].

Biological context of Skimmetin

• Focal electrical stimulation of the cortex resulted in a rapid vasodilation (50% dilation = 1-3 s) of pial arterioles and venules and an increase in Um clearance. pHi showed no significant change until around 10 s [10].
• Ethoxycoumarin was metabolized by isolated epidermal cells via dealkylation to 7-hydroxycoumarin (7-OHC) and subsequent conjugation [11].
• Sex difference in the O-dealkylation activity of 7-hydroxycoumarin O-alkyl derivatives in liver microsomes of rats [12].
• 7-Hydroxycoumarin at the concentration of 160 microg/ml (1 mM), inhibited the G(1)/S transition of the cell cycle, an action consistent with the cytostatic effect [2].
• Inhibition studies with 7-hydroxycoumarin revealed that an approximately four times higher molar concentration of the derivative was necessary to cause 50% displacement of coumarin from its binding site [13].

Anatomical context of Skimmetin

• Double pre-treatments of mouse skin with AUR, but not UMB, markedly suppressed edema formation, hydrogen peroxide production, leukocyte infiltration, and the rate of proliferating cell nuclear antigen-stained cells [14].
• Furthermore, the rate of conjugation of 7-hydroxycoumarin was significantly elevated in liver cells isolated from beta-naphthoflavone treated fish when compared with the control rate [15].
• Umbelliferone as an Intracellular pH-sensitive fluorescent indicator and blood-brain barrier probe: instrumentation, calibration, and analysis [16].
• Conjugation and excretion of metabolites of 7-hydroxycoumarin in the small intestine of rats and guinea-pigs [17].
• The data indicate that sulfation of 7-hydroxycoumarin proceeds at almost maximal rates in kidney tubule fragments at physiological serum sulfate concentrations [18].

Associations of Skimmetin with other chemical compounds

• The production of 7-hydroxycoumarin, the O-dealkylation product, by the wild-type enzyme exhibited a rank order of C2 > C4 > C3 > C1 > C5 > C6 = C7 [19].
• In isolated liver cells, 90% of the 7-hydroxycoumarin formed from deethylation of 7-ethoxycoumarin was further metabolized to conjugated products [15].
• In cylindrical gel entrapment cultures, hepatocyte growth factor caused a significant increase in 2-day viability but had no effect on the metabolite appearance of lidocaine or 4-methyl umbelliferone or albumin production [20].
• Six alkyl ethers of 7-hydroxycoumarin, ranging from methoxy- to hexoxycoumarin, were studied for their NADPH-dependent metabolism by liver microsomes of male rats treated with phenobarbital (PB) or 3-methyl-cholanthrene (MC) [21].
• 5. The S. aureus lipase has a narrow substrate specificity: short-chain triacylglycerols and acyl esters of both p-nitrophenol and umbelliferone are readily degraded, whereas medium- and long-chain lipids, as well as phospholipids, are poor substrates [22].

Gene context of Skimmetin

• The 7-hydroxycoumarin sulfotransferase activity of the slices decreased significantly more slowly than did the P450 activities [23].
• CYP2A6 is the only enzyme catalysing this reaction and consequently the formation of 7-hydroxycoumarin can be used as 'an in vitro and in vivo probe' for CYP2A6 [24].
• 86% for CYP2Cl9, 90% for CYP2D6, 164% for CYP3A4, 76% for UDP-glucuronidase, and 88% for umbelliferone sulfotransferase [25].
• The major coumarin metabolite formed by CYP2A13 was 7-hydroxycoumarin, which accounted for 43% of the total metabolism [26].
• Knowledge of the decrease of cyclin D1 by 7-hydroxycoumarin may lead to its use in cancer therapy, as well as to the development of more active compounds [2].

Analytical, diagnostic and therapeutic context of Skimmetin

• We examined the relationship of ICT with perfusion, as imaged quantitively using umbelliferone clearance (CBF(umb)) [27].
• Rapid and sensitive determination of coumarin and 7-hydroxycoumarin and its glucuronide conjugate in urine and plasma by high-performance liquid chromatography [28].
• Development of an antibody-based amperometric biosensor to study the reaction of 7-hydroxycoumarin with its specific antibody [29].
• A novel method for the determination of 7-hydroxycoumarin in human urine which combines thin-layer chromatography (TLC) with fluorescence detection (FD) has been devised [30].
• Serum theophylline determination by fluorescence polarization immunoassay utilizing an umbelliferone derivative as a fluorescent label [31].

References