Human exposure to coumarin continues despite controversy over its hepatotoxic potential. Greater understanding of human reactions to coumarin may be achieved by studying murine interstrain differences. The metabolic basis of coumarin hepatotoxicity and its modulation by liver enzyme inducers, beta-naphthoflavone (beta NF) and aroclor 1254 (ARO), were investigated in C3H/He and DBA/2 mice. Couma...

Cytochrome P450 (P450) 2A6 is an important human enzyme involved in the metabolism of many xenobiotic chemicals including coumarin, indole, nicotine, and carcinogenic nitrosamines. A combination of random mutagenesis and high-throughput screening was used in the analysis of P450 2A6, utilizing a fluorescent coumarin 7-hydroxylation assay. The steady-state kinetic parameters (k(cat) and Km) for ...

A novel short-step methodology for the synthesis in good yields of functionalized coumarins has been developed starting from an activated precursor, the N-hydroxysuccinimide ester of O-acetylsalicylic acid. The procedure is based on a tandem C-acylation-cyclization process under mild reaction conditions. The structure of 3-methoxycarbonyl-4-hydroxy coumarin has been established by X-ray diffrac...

Silybin, a major constituent of the milk thistle, is used to treat several liver disorders. Silybin inactivated purified, recombinant cytochromes P450 (P450) 3A4 and 2C9 in a mechanism-based manner. The inactivations were time-, concentration-, and NADPH-dependent. The inactivation of the 7-benzyloxy-4-(trifluoromethyl-)coumarin O-debenzylation activity (P450 3A4) was characterized by a K(I) of...

ABSTRACT A new series of hydroxycoumarin derivatives has been synthesized using conventional synthesis. The syntheses were accelerated by microwave assistance. Yields in both cases were comparable (59-69 %). The structures were established by 1H and 13C NMR spectroscopy and high-resolution mass spectrometry. Five compounds (5-hydroxy-4,7-dimethylcoumarin, 6-acetyl-5-hydroxy-4,7-dimethylcoumarin...

Some novel coumarins were synthesized starting from 4-hydroxycoumarin and methyl bromoacetate. The structures of the newly obtained compounds were confirmed by elemental analysis, mass, IR and NMR spectra.

In this work, a multifunctional yellowing inhibitor was synthesized by the Pechmann method. In order to obtain the target compound, 7-hydroxy-4methyl coumarin was prepared by using the raw materials of resorcinol and ethyl acetoacetate, with toluene-p-sulfonic acid as the catalyst. New polymeric fluorescent compounds were synthesized by connecting the 7hydroxy-4-methyl coumarin, the hindered am...

Coumarin is used widely as a fragrance constituent and is administered clinically in the treatment of certain lymphedemas and malignancies. Although toxicity occurs only rarely in humans treated clinically with high-dose coumarin, it is well established that coumarin is hepatotoxic in the rat. This species difference in susceptibility to toxicity reflects the disparate metabolic processes occur...