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 ...

Coumarin was previously found to cause tissue-selective toxicity in the olfactory mucosa (OM) of rats and mice, with rats being the more sensitive species. The aim of this study was to explore the role of target tissue biotransformation in OM-selective toxicity and the metabolic basis of the species differences in coumarin toxicity. At least six coumarin metabolites were detected in OM microsom...

Irosustat is a novel steroid sulfatase inhibitor for hormone-dependent cancer therapy. Its structure is a tricyclic coumarin-based sulfamate that undergoes desulfamoylation in aqueous solution, yielding the sulfamoyl-free derivative, 667-coumarin. The aim of the present work was to study the in vitro metabolism of irosustat, including its metabolic profile in liver microsomes and hepatocytes, t...

A new sustainable green protocol for obtaining polyethylene glycol (PEG) conjugates, with a prototype molecule, which in this work was coumarin, by means of click chemistry is presented. The organic solvents commonly used type reaction were replaced supercritical carbon dioxide (scCO2). synthesis and characterization PEG-coumarin successfully reported using FTIR, 1H NMR, MALDI TOF. Subsequently...

A new eudesmane-type sesquiterpene, 11-hydroxycapitulatin B (1), along with a known related sesquiterpene, capitulatin B (2), was isolated from the endophytic fungus Nigrospora oryzae A8 from Aquilaria sinensis, the only plant resource for agarwood production in China. This research demonstrates that the endophytic fungi from A. sinensis might play a role in the formation of agarwood.

A transformed root culture of Cichorium intybus L. (Asteraceae) was found to produce sesquiterpene lactones of guaiane and germacrane type. Lactucopicrin, 8-desoxylactucin and three sesquiterpene lactone glycosides: crepidiaside B, sonchuside A and ixerisoside D were isolated from the roots. The yield of 8-desoxylactucin reached 0.03 g l(-1) at the early stationary phase of the culture.

The epimeric sesquiterpene alcohols (14R)-beta-oplopenol and (14S)-beta-oplopenolwere obtained by LiAlH(4) reduction of beta-oplopenone. The complete (1)H- and (13)C-NMR assignments of these two new sesquiterpene alcohols have been made using 1D and 2D NMR techniques, including COSY, NOESY, HSQC, HMBC experiments.

Lipids and coumarin were extracted from cumaru seeds using Soxhlet extraction (SE) with ethanol (EtOH) ethyl acetate (EtOAc), scCO 2 , +EtOH +EtOAc, either in a single or sequential stages, PLE EtOH. ScCO +EtOAc provided yields 28% to 31%, independently of the conditions employed, provide top yield 38%, at 25 MPa 80 ºC. Extraction enhanced by three extractions, resulting 44.0% 56.5% for +EtOH, ...

Coumarin derivatives, such as warfarin, acenocoumarol and phenprocoumon, are commonly prescribed as oral anticoagulants for the treatment of thromboembolic disorders. Therapy with coumarin derivatives is most effective when the international normalized ratio (INR) is kept within a narrow range. Prescribing of these drugs is difficult because of their narrow therapeutic window and the wide inter...

Coumarin-induced mouse Clara cell toxicity is thought to result from the local formation of coumarin 3,4-epoxide (CE). However, this toxicity is not observed in the rat, indicating species differences in coumarin metabolism. The purpose of the present work was to characterize the in vitro kinetics of coumarin metabolism in mouse, rat, and human whole lung microsomes, and to determine whether sp...