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1.
Indian J Physiol Pharmacol ; 2000 Jan; 44(1): 50-6
Article Dans Anglais | IMSEAR | ID: sea-106293

Résumé

In an attempt to develop effective antidote against organophosphorus intoxication, some new imidazole-pyridinium mono-oximes, long chain pyridinium mono-oximes and cholineacetyltransferase inhibitors were synthesised. These compounds were evaluated for their in vivo therapeutic protection and neuromuscular function studies in rodents. The results indicate that SPK-series oximes may be useful against sarin poisoning without any beneficial effect against VX (O-Ethyl S-2-NN-diisopropylaminoethyl methylphosphonofluoridate) intoxication. The cholineacetyltransferase (ChAT) inhibitors may not be of any help against any of the OP compounds studied in this study.


Sujets)
Animaux , Antidotes/synthèse chimique , Choline O-acetyltransferase/antagonistes et inhibiteurs , Anticholinestérasiques/toxicité , Antienzymes/synthèse chimique , Dose létale 50 , Mâle , Souris , Jonction neuromusculaire/effets des médicaments et des substances chimiques , Composés organiques du phosphore/antagonistes et inhibiteurs , Composés organothiophosphorés/toxicité , Oximes/synthèse chimique , Composés de pyridinium/synthèse chimique , Rats , Rat Wistar , Sarin/toxicité
2.
Indian J Biochem Biophys ; 1991 Oct-Dec; 28(5-6): 381-8
Article Dans Anglais | IMSEAR | ID: sea-28628

Résumé

The mechanism of interaction of methoxyamine with sheep liver serine hydroxymethyltransferase (EC 2.1.2.1) (SHMT) was established by measuring changes in enzyme activity, visible absorption spectra, circular dichroism and fluorescence, and by evaluating the rate constant by stopped-flow spectrophotometry. Methoxyamine can be considered as the smallest substituted aminooxy derivative of hydroxylamine. It was a reversible noncompetitive inhibitor (Ki = 25 microM) of SHMT similar to O-amino-D-serine. Like in the interaction of O-amino-D-serine and aminooxyacetic acid, the first step in the reaction was very fast. This was evident by the rapid disappearance of the enzyme-Schiff base absorbance at 425 nm with a rate constant of 1.3 x 10(3) M-1 sec-1 and CD intensity at 430 nm. Concomitantly, there was an increase in absorbance at 388 nm (intermediate I). The next step in the reaction was the unimolecular conversion (1.1 x 10(-3) sec-1) of this intermediate to the final oxime absorbing at 325 nm. The identity of the oxime was established by its characteristic fluorescence emission at 460 nm when excited at 360 nm and by high performance liquid chromatography. These results highlight the specificity in interactions of aminooxy compounds with sheep liver serine hydroxymethyltransferase and that the carboxyl group of the inhibitors enhances the rate of the initial interaction with the enzyme.


Sujets)
Animaux , Sites de fixation , Glycine hydroxymethyltransferase/métabolisme , Hydroxylamines , Cinétique , Foie/enzymologie , Phosphate de pyridoxal , Bases de Schiff , Ovis
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