14307-83-6Relevant academic research and scientific papers
Isotope-labeled differential profiling of metabolites using N-benzoyloxysuccinimide derivatization coupled to liquid chromatography/high-resolution tandem mass spectrometry
Wagner, Michel,Ohlund, Leanne B.,Shiao, Tze Chieh,Vézina, Amélie,Annabi, Borhane,Roy, René,Sleno, Lekha
, p. 1632 - 1640 (2015/11/16)
Rationale An isotopic labeling strategy based on derivatizing amine-containing metabolites has been developed using light (12C6) and heavy (13C6) N-benzoyloxysuccinimide reagents for semi-targeted metabolomic applications. Methods Differentially labeled samples were combined and analyzed simultaneously by liquid chromatography/high-resolution tandem mass spectrometry (LC/HR-MS/MS) to compare relative amounts of amine-containing metabolites. The selectivity of the reaction was determined with model metabolites and was shown to also be applicable to thiol and phenol moieties. The potential for relative quantitation was evaluated in cell extracts and the method was then applied to quantify metabolic perturbations occurring in human cultured cells under normal vs. oxidative stress conditions. Results A total of 279 derivatized features were detected in HL60 cell extracts, 77 of which yielded significant concentration changes upon oxidative stress treatment. Based on accurate mass measurements and MS/MS spectral matching with reference standard solutions, 10 metabolites were clearly identified. Derivatized compounds were found to have diagnostic fragment ions from the reagent itself, as well as structurally informative ions useful for metabolite identification. Conclusions This simple derivatization reaction can be applied to the relative quantitation of amine-, thiol- and phenol-containing compounds, with improved sensitivity and chromatographic peak shapes due to the increased hydrophobicity of polar metabolites not readily amenable to reversed-phase LC/MS analysis.
Design, synthesis, and preliminary pharmacological evaluation of N-Acyl-3-aminoglutarimides as broad-spectrum chemokine inhibitors in vitro and anti-inflammatory agents in vivo
Fox, David J.,Reckless, Jill,Warren, Stuart G.,Grainger, David J.
, p. 360 - 370 (2007/10/03)
A series of N-substituted 3-aminoglutarimides have been synthesized and tested for inhibitory activity against a range of chemokines in vitro and for suppression of lipopolysaccharide-induced inflammation in vivo. The results show that they represent the first class of small molecules with broad-spectrum chemokine inhibitory effects. Among the compounds studied, 10 (NR58,4) was the most potent, being active at doses between 5 and 15 nM in vitro and at 0.3 mg kg-1 in vivo.
Synthesis, spectroscopic characterization, stability assessment and DNA-binding of new 2,6-piperidinedione derivatives
Abou-Zeid, Laila,El-Mowafy, Abdalla M,El-Kerdawy, Mohammed M,Hamza, Huda,Abdel-Hamid, Mohammed E
, p. 763 - 770 (2007/10/03)
This work reports on structural characterization of new antineoplaston (ANP) representatives, namely 3-(benzoylamino)-2,6-piperidinedione (BPD), 3-(4-methoxybenzoylamino)-2,6-piperidinedione (MPD) and 3-(p-nitrobenzoylamino)-2,6-piperidinedione (NPD). The
The utilization of alanine, glutamic acid, and serine as amino acid substrates for glycine N-acyltransferase.
van der Westhuizen,Pretorius,Erasmus
, p. 102 - 109 (2007/10/03)
The conjugation of benzoyl-CoA with the aliphatic and acidic amino acids by glycine N-acyltransferase, as well as the amides of the latter group, was investigated. Bovine and human liver benzoyl-amino acid conjugation were investigated using electrospray ionization tandem mass spectrometry (ESI-MS-MS). Bovine glycine N-acyltransferase catalyzed conjugation of benzoyl-CoA with Gly (Km(Gly) = 6.2 mM), Asn (Km(Asn) = 129 mM), Gln (Km(Gln) = 353 mM), Ala (Km(Ala) = 1573 mM), Glu (Km(Glu) = 1148 mM) as well as Ser in a sequential mechanism. In the case of the human form, conjugation with Gly (Km(Gly) = 6.4 mM), Ala (Km(Ala) = 997 mM), and Glu was detected. The presence of these alternative conjugates did not inhibit bovine glycine N-acyltransferase activity significantly. Considering the relatively low levels at which these conjugates are formed, it is unlikely that they will have a significant contribution to acyl-amino acid conjugation under normal conditions in vivo. However, their cumulative contribution to acyl-amino acid conjugation under metabolic disease states may prove to have a useful contribution to detoxification of elevated acyl-CoAs.
Enantiomeric Enrichment in the Hydrolysis of Oxazolones Catalyzed by Cyclodextrins or Proteolytic Enzymes
Daffe, V.,Fastrez, J.
, p. 3601 - 3605 (2007/10/02)
Five 5(4H)-oxazolones bearing substituents of variable hydrophobicity and bulkiness in positions 2 and 4 have been hydrolyzed in the presence of the proteolytic enzymes chymotrypsin and subtilisin or the α- and β-cyclodextrins.The acylamino acids produced are partially deracemized.With the enzymes, an appreciable enantiomeric enrichment is obtained only when both substituents are relatively bulky; the enantioselectivities are nevertheless quite low for enzymic reactions.With chymotrypsin, an enantiomeric excess of 76percent in favor of the L isomer is observed in the hydrolysis of the 2-phenyl-4-benzyloxazolone and of 30percent in favor of the D for the 2-phenyl-4-(2-carboxamidoethyl)oxazolone.There is a general inversion of stereoselectivity between chymotrypsin and subtilisin.The hydrolysis in the presence of cyclodextrin is a multistep process with formation of an acylcyclodextrin intermediate concurrent with hydrolysis.The substituent in position 2 plays an important role in controlling the enantioselectivity.When this substituent is a phenyl, the L acylamino acid is the predominant product with an enantiomeric excess of the order of 60percent.When there is a methyl in position 2, the direction of asymmetric induction is reversed or the optical yield is close to zero.
