RESUMO
Rat liver tissue homogenates were utilized for in vitro enzymatic conversion of 2,6-diethylaniline (DEA) to the important alachlor metabolite 4-amino-3,5-diethylphenyl sulfate (ADEPS), which was also generated as a radiolabeled standard for use in metabolism studies. ADEPS formation in rodents is associated with the production of other reactive metabolites implicated in alachlor rodent carcinogenesis, making dependable access to an ADEPS standard highly desirable. (14)C-DEA was oxidized by rat liver microsomes to (14)C-4-amino-3,5-diethylphenol, which was further converted to ADEPS via addition of the phosphosulfate transferase cofactor adenosine-3'-phosphate-5'-phosphosulfate. Microprobe NMR was used in conjunction with high-resolution mass spectrometry to fully characterize the resulting (14)C-ADEPS and confirm its structure. Because microgram quantities sufficed for full characterization, the enzymatic transformation provides a viable alternative to radiosynthesis of (14)C-ADEPS.
Assuntos
Acetamidas/farmacocinética , Alcanos/metabolismo , Compostos de Anilina/química , Herbicidas/farmacocinética , Fígado/metabolismo , Sulfatos/metabolismo , Alcanos/síntese química , Animais , Biotransformação , Radioisótopos de Carbono , Ratos , Sulfatos/síntese química , Ésteres do Ácido SulfúricoRESUMO
The metabolism of alachlor was studied using in vitro incubations with microsomal fractions prepared from liver and nasal turbinates of rats and mice. Specifically, the transformation of alachlor to 3,5-diethylbenzoquinone-4-imine was examined. A key intermediate in this pathway was identified as 2,6-diethylaniline, the formation of which required catalysis by microsomal arylamidases. 2,6-Diethylaniline was oxidized to 4-amino-3,5-diethylphenol and the electrophilic 3,5-diethylbenzoquinone 4-imine. Rat nasal tissue possessed high enzymatic activity which can promote the formation of the reactive quinone imine. Whole body autoradiographic analysis demonstrated localization of radioactivity in the rat nasal tissue following oral administration of alachlor. A methylsulfide metabolite of alachlor was shown to be a precursor to 2,6-diethylaniline. The deposition of radioactivity in the rat nasal tissue was more pronounced following oral administration of the methylsulfide metabolite of alachlor.
Assuntos
Acetamidas/metabolismo , Fígado/metabolismo , Conchas Nasais/metabolismo , Acetamidas/farmacocinética , Administração Oral , Aminopeptidases/metabolismo , Animais , Autorradiografia , Biotransformação , Técnicas In Vitro , Fígado/enzimologia , Masculino , Camundongos , Mucosa Nasal/metabolismo , Oxirredução , Ratos , Especificidade da Espécie , Especificidade por SubstratoRESUMO
An antibiotic-producing pseudomonad was isolated from a seawater sample from a La Jolla, Calif., tidepool. The pseudomonad produces two novel antibacterial compounds, 2-n-pentyl-4-quinolinol and 2-n-heptyl-4-quinolinol. It also synthesizes indole-3-carboxaldehyde, 6-bromoindole-3-carboxaldehyde, and the known antibiotic p-hydroxybenzaldehyde. Each of these compounds was identified by analysis of spectral data, and the structures were confirmed by synthesis or comparison with authentic samples.
