RESUMEN
Kojic acid (5-hydroxy-2-hydroxymethyl-4-pyranone) represents an attractive polyfunctional skeleton for development of biologically active compounds. The authors prepared a great variety of kojic acid derivatives and selected biological properties have been studied. Thus, kojic acid derivatives are promising compounds that might advantageously be used in human and/or veterinary medicine and also in preparation of new, even more biologically active preparations.
Asunto(s)
Antifúngicos/síntesis química , Antineoplásicos/síntesis química , Pironas/química , Pironas/farmacología , Animales , Antifúngicos/farmacología , Antineoplásicos/farmacología , Humanos , Leucemia L1210/tratamiento farmacológicoRESUMEN
An analytical method, based on a selective extraction and pyrolysis gas chromatography/mass spectrometry assay of arsenocholine and acetylarsenocholine in aquatic organisms, is described. Characteristic fragmentation patterns were obtained from pyrolytically demethylated compounds. The molecules were rearranged in unique pathways which differed from those of corresponding nitrogen analogues. Qualitative determination of arsenocholine and acetylarsenocholine was achieved by gas chromatographic as well as mass spectrometric analysis of the thermal degradation products (trimethylarsine, dimethylvinylarsine and the demethylated arsenocholine or acetylarsenocholine). Arsenocholine and acetylarsenocholine in fish from industrially polluted water were isolated and identified. Massfragmentographic quantification of the arsenic compounds in fish was carried out by use of deuterium labelled analogues of arsenocholine and acetylarsenocholine as internal standards. The method showed a high sensitivity.
Asunto(s)
Arsenicales/análisis , Colina/análogos & derivados , Peces/metabolismo , Contaminantes Químicos del Agua/análisis , Contaminantes del Agua/análisis , Animales , Arsenicales/metabolismo , Colina/análisis , Colina/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Músculos/metabolismoRESUMEN
Vitamin A has been shown to affect the in vitro metabolism of 2AAF. At low concentrations of retinol or retinyl palmitate, a decreased production of ring-hydroxylated as well as deacetylated and N-hydroxylated metabolites was observed, measured by high performance liquid chromatography. The increased mutagenicity of 2AAF observed after addition of vitamin A in the Ames test cannot therefore be explained as a result of stimulated N-hydroxylation. However, the addition of retinol was found to enhance the mutagenicity of the metabolite N-OH-2AAF in the presence of an S-9 fraction of rat liver homogenate. No differences with regard to the covalent binding of 2AAF or its metabolites to rat liver DNA/RNA in vivo could be demonstrated in animals fed diets with normal or high vitamin A content.
Asunto(s)
2-Acetilaminofluoreno/metabolismo , Vitamina A/farmacología , 2-Acetilaminofluoreno/farmacología , Animales , Biotransformación/efectos de los fármacos , ADN/metabolismo , Técnicas In Vitro , Hígado/efectos de los fármacos , Hígado/metabolismo , Mutágenos , ARN/metabolismo , Ratas , Ratas EndogámicasRESUMEN
The mechanism of cytochrome P-450 catalyzed steroid hydroxylations in rat liver microsomes has been investigated by employing derivatives of iodosylbenzene as oxygen donors. The model steroid substrate androstenedione which was hydroxylated in positions 7 alpha, 6 beta, and 16 alpha was used in reactions supported by NADPH, iodosylbenzene, and iodosylbenzene derivatives. Evidence for cytochrome P-450 involvement in iodosylbenzene-sustained androstenedione hydroxylation included inhibition by substrates and modifiers of cytochrome P-450. The most efficient oxygen donors were (diacetoxyiodo)-2-nitrobenzene greater than (diacetoxyiodo)-2-chlorobenzene greater than 2-nitroiodosylbenzene greater than (dinitratoiodo)-2-nitrobenzene greater than (diacetoxyiodo)benzene greater than (diacetoxyiodo)-2-methoxybenzene greater than 4-(diacetoxyiodo)toluene greater than iodosylbenzene. The capacity of the oxidation agents to serve as oxygen donors in cytochrome P-450 dependent steroid hydroxylation is probably dependent upon several factors such as the tendency of iodosyl compounds to associate, which decreases coordination with the heme iron, the presence of bulky substituents in the 2 position (decreases association), and the presence of electron-withdrawing substituents (tends to decrease coordination with the heme iron). The rates of 7 alpha, 6 beta, and i6 alpha hydroxylation of androstenedione catalyzed by (diacetoxyiodo)-2-nitrobenzene were 108-, 130-, and 167-fold higher, respectively, than the rates of the NADPH-supported reactions. These results strongly suggest that the rate-limiting step in NADPH-sustained cytochrome P-450 catalyzed reactions is the rate of reduction of cytochrome P-450.