Male-specific metabolism of simvastatin by rat liver microsomes

Simvastatin was more effectively metabolized by the liver microsomes of male rats than females. The sex difference appeared in the composition of the metabolites. Two male-specific metabolites were identified by NMR and mass spectrometry as 3'-hydroxy and 3',3'-dihydroxy-delta 4',5' derivatives of simvastatin.     

Regioselective N-acetylation as a route of nitro-9-phenylenediamine metabolism by rat liver cytosol

Regioselectivity in N-acetylation of nitro-0-phenylenediamine, a widely used hair dye component, by rat liver cytosolic N-acetyltransferases was studied in relation to its substituent effects on enzymatic N-acetylation of mono-substituted anilines. Nitro-p-phenylenediamine was acetylated specifically at the N4-position to afford the N4-monoacetate, a major urinary metabolite in the rat, when incubated with rat liver cytosol fortified with acetyl-coenzyme A. N1-Acetylation of nitro-p-phenylenediamine did not take place even when the N4-monoacetate was used as a substrate, suggesting a strong steric hindrance effect of the ortho nitro group on the enzymatic N1-acetylation. The steric hindrance effect of the nitro group on the cytosolic N-acetylation of the ortho amino group was revealed by a comparative study carried out by using aniline, three respective regioisomers of nitroanilines and phenylenediamines as model substrates. The comparative study also indicated the enzymatic N-acetylation of the mono-substituted anilines to be strongly influenced by the electronic effect of the substituents. Regioselective N-acetylation in the hepatic cytosol was also investigated with N1- and N4-monoacetates of 1,2,4-triaminobenzene. The monoacetates yielded the N1,N4-diacetate, another major urinary metabolite of the hair dye component, in the rat, without concomitant formation of the N2,N4-diacetate or the N1,N2,N4-triacetate. The triacetate was formed only from the N1,N2-diacetate in the enzymatic reactions. A comparative study, carried out by using N-mono-acetates of three regioisomeric phenylenediamines, indicated that the N-acetyl group had a potent steric hindrance effect on the primary amino group at the ortho position.(ABSTRACT TRUNCATED AT 250 WORDS)     

Toremifene metabolism in rat,mouse and human liver microsomes: identification of alpha-hydroxytoremifene by LC-MS

The in vitro metabolism of toremifene has been studied in liver microsomal preparations from rat, mouse and human sources using high-performance liquid chromatography-electrospray ionisation mass spectrometry (HPLC-ESIMS). The metabolites detected were N-desmethyltoremifene (m/z 392), 4-hydroxytoremifene (m/z 422), 4'-hydroxytoremifene (m/z 422) and toremifene N-oxide m/z 422). In addition, a new polar metabolite with a protonated molecule at m/z 422 has been detected in all three species. The compound was identified by tandem MS-MS as alpha-hydroxytoremifene, an analogue of alpha-hydroxytamoxifen. The results showed that alpha-hydroxylation is a common feature of tamoxifen and toremifene metabolism and that alpha-hydroxytamoxifen is unlikely to be the reactive metabolite responsible for the hepatocarcinogenesis in rat, as widely believed.     

Reductive 2,6-trans-diallylation of pyridine by triallylborane

Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2644–2645, November, 1991.     

Reductive hetarylation OF imines by thioxanthene

D. I. Pryanishnikov Perm Agricultural Institute, 614000 Perm. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1003–1005, July, 1995. Original article submitted December 2, 1994.     

Reductive amination ofl-menthol by aliphatic nitriles

The reductive amination ofl-menthol with aliphatic nitriles has been studied. A probable scheme of the mechanism of the reaction has been put forward and the stereochemical composition of its products has been determined. It has been established with the aid of the¹³C NMR method that the reaction forms a mixture of isomeric optically-active N-alkylmenthyl-, -neomenthyl-, -isomenthyl-, and-neoisomenthyl-amines in a ratio of 54:24:17:5. The absolute configurations of the amines obtained have been determined.     

Reductive decyanation of pyridinecarbonitriles by titanium trichloride

Titanium(III) chloride promotes reductive decyanation of 4-CN- and 2-CN-pyridine. The role of complex forming agents is discussed.     

利用还原性多糖合成银纳米粒子

利用还原性多糖为稳定剂、AgNO₃为前驱物, 通过一条绿色途径合成银纳米粒子, 并探讨了纳米粒子的形成机理. 对多糖高浓度时制得的复合物在空气与氮气气氛下进行了热处理, 分别得到了银的大孔海绵体与银纳米粒子/碳的复合材料. 对产物进行了X射线衍射(XRD)、扫描电子显微镜(SEM)、透射电子显微镜(TEM)、紫外-可见分光光度(UV-vis)以及BET吸附表征.     

Reductive activation of mitomycin A by thiols

[reaction: see text]. Mitomycin C is unchanged upon exposure to thiols under physiological conditions. Its more toxic variant, mitomycin A (MA), undergoes elimination of methanol to give a variety of mitosene derivatives, diagnostic of its activation to a reactive electrophile. Evidence is presented for a novel reductive mechanism, characterized by the transient addition of a thiol to the quinone of MA, followed by intramolecular electron transfer, leading to reduced quinone and oxidized thiol.     

Study the pharmacokinetics of AV-45 in rat plasma and metabolism in liver microsomes by ultra-performance liquid chromatography with mass spectrometry

An ultra‐performance liquid chromatography–tandem mass spectrometric (UPLC‐MS/MS) method was developed and validated to determine AV‐45 in rat plasma. After the addition of the internal standard benzophenone, plasma samples were pretreated by protein precipitation. Chromatographic separation was achieved on an Acquity UPLC BEH C₁₈ column (50 × 2.1 mm, 1.7 µm) by gradient elution at a flow rate of 0.4 mL/min. Detection of analytes and internal standard (IS) was done by tandem mass spectrometry, operating in positive‐ion and multiple reaction monitoring mode. The method was fully validated for its sensitivity, selectivity, accuracy and precision, matrix effect and stability study. The calibration curve showed good linearity over the concentration range 2.00–1000 ng/mL for AV‐45. Intra‐ and inter‐day precisions were less than 7.6%, and accuracy ranged from 100.6 to 107.8%. There was no matrix effect. The validated method was successfully applied to a pharmacokinetic study of AV‐45 in rats. Additionally, the metabolism of AV‐45 in rat liver microsomes was also studied by ultra‐performance liquid chromatography combined with time‐of‐flight mass spectrometry (UPLC/TOF‐MS). With the help of chromatographic behavior and accurate mass measurements, the metabolites were characterized. Copyright © 2011 John Wiley & Sons, Ltd.