538-69-2Relevant academic research and scientific papers
Production of new amilorides as potent inhibitors of mitochondrial respiratory complex I
Murai, Masatoshi,Habu, Sayako,Murakami, Sonomi,Ito, Takeshi,Miyoshi, Hideto
, p. 1061 - 1066 (2015/10/05)
Amilorides, well-known inhibitors of Na+/H+ antiporters, have also shown to inhibit bacterial and mitochondrial NADH-quinone oxidoreductase (complex I). Since the membrane subunits ND2, ND4, and ND5 of bovine mitochondrial complex I
Expression in yeast, new substrates, and construction of a first 3D model of human orphan cytochrome P450 2U1: Interpretation of substrate hydroxylation regioselectivity from docking studies
Ducassou, Lionel,Jonasson, Gabriella,Dhers, Laura,Pietrancosta, Nicolas,Ramassamy, Booma,Xu-Li, Yun,Loriot, Marie-Anne,Beaune, Philippe,Bertho, Gildas,Lombard, Murielle,Mansuy, Daniel,André, Fran?ois,Boucher, Jean-Luc
, p. 1426 - 1437 (2015/04/27)
Abstract Background Cytochrome P450 2U1 (CYP2U1) has been identified from the human genome and is highly conserved in the living kingdom. In humans, it has been found to be predominantly expressed in the thymus and in the brain. CYP2U1 is considered as an orphan enzyme as few data are available on its physiological function(s) and active site topology. Its only substrates reported so far were unsaturated fatty acids such as arachidonic acid, and, much more recently, N-arachidonoylserotonin. Methods We expressed CYP2U1 in yeast Saccharomyces cerevisiae, built a 3D homology model of CYP2U1, screened a library of compounds known to be substrates of CYP2 family with metabolite detection by high performance liquid chromatography-mass spectrometry, and performed docking experiments to explain the observed regioselectivity of the reactions. Results We show that drug-related compounds, debrisoquine and terfenadine derivatives, subtrates of CYP2D6 and CYP2J2, are hydroxylated by recombinant CYP2U1 with regioselectivities different from those reported for CYP2D6 and 2J2. Docking experiments of those compounds and of arachidonic acid allow us to explain the regioselectivity of the hydroxylations on the basis of their interactions with key residues of CYP2U1 active site. Major conclusion Our results show for the first time that human orphan CYP2U1 can oxidize several exogenous molecules including drugs, and describe a first CYP2U1 3D model. General significance These results could have consequences for the metabolism of drugs particularly in the brain. The described 3D model should be useful to identify other substrates of CYP2U1 and help in understanding its physiologic roles.
N1- and N2-Substituted 2-Amino-5,6-dihydro-4(1H)-pyrimidinones (Heterocyclic Compounds, 79)
Wendelin, Winfried,Riedl, Renate
, p. 237 - 252 (2007/10/02)
The reactions of the monosubstituted guanidines 2b-h with methyl acrylate in dimethylformamide or ethanol as solvent preferentially afford 1-substituted 2-amino-5,6-dihydro-4(1H)-pyrimidinones 6b-h.The structures of 1-hexyl- and 1-benzyl-4-pyrimidinones 6c, e and of the picrate of 1-phenylpyrimidinone 6g were proved by comparison with authentic samples, which were prepared from N-substituted ethyl 3-amino-propionates 14c, e and g and cyanamide.Accordingly, 6g is not identical with authentic 2-phenylaminopyrimidinone 7g (prepared from 2-methylthio-4-pyrimidinone 10 and 2-thioxo-4-pyrimidinone 12 respectively, compare.N,N-Disubstituted guanidines 2i-m react with methyl acrylate in dimethylformamide as solvent to afford N2,N2-disubstituted 2-amino-5,6-dihydro-4-(1H)-pyrimidinones 7i-m.Action of morpholine-4-carboxamidine (2l) on methyl acrylate in ethanol yields 2-morpholinopyrimidinone 7l as byproduct and 3-ethoxy-N-propionamide (9l) as mainproduct.Keywords: Acrylic acid methylester, reactions; Guanidines, mono- and N,N-disubstituted; Propionamide, 3-ethoxy-N-; 4(1H)-Pyrimidinones, 2-amino; Pyrimidine-1-propionic acid ethylester, hexahydro-4-oxo-2-thioxo
