Epoxy compounds usually have stronger nucleophilic ability, because the alkyl group on the oxygen atom makes the bond angle smaller, which makes the lone pair of electrons react more dissimilarly with the electron-deficient system. Compound: 4-Hydroxyquinoline-2-carboxylic Acid, is researched, Molecular C10H7NO3, CAS is 492-27-3, about Kynurenic acid and its analogue SZR-72 ameliorate the severity of experimental acute necrotizing pancreatitis.Recommanded Product: 492-27-3.
The pathophysiol. of acute pancreatitis (AP) is not well understood, and the disease does not have specific therapy. Tryptophan metabolite L-kynurenic acid (KYNA) and its synthetic analog SZR-72 are antagonists of the N-methyl-D-aspartate receptor (NMDAR) and have immune modulatory roles in several inflammatory diseases. Our aims were to investigate the effects of KYNA and SZR-72 on exptl. AP and to reveal their possible mode of action. AP was induced by i.p. (i.p.) injection of L-ornithine-HCl (LO) in SPRD rats. Animals were pretreated with 75-300 mg/kg KYNA or SZR-72. Control animals were injected with physiol. saline instead of LO, KYNA and/ or SZR-72. Laboratory and histol. parameters, as well as pancreatic and systemic circulation were measured to evaluate AP severity. Pancreatic heat shock protein-72 and IL-1b were measured by western blot and ELISA, resp. Pancreatic expression of NMDAR1 was investigated by RT-PCR and immunohistochem. Viability of isolated pancreatic acinar cells in response to LO, KYNA, SZR-72 and/or NMDA administration was assessed by propidium-iodide assay. The effects of LO and/or SZR-72 on neutrophil granulocyte function was also studied. Almost all investigated laboratory and histol. parameters of AP were significantly reduced by administration of 300 mg/kg KYNA or SZR-72, whereas the 150 mg/kg or 75 mg/kg doses were less or not effective, resp. The decreased pancreatic microcirculation was also improved in the AP groups treated with 300 mg/kg KYNA or SZR-72. Interestingly, pancreatic heat shock protein-72 expression was significantly increased by administration of SZR-72, KYNA and/or LO. mRNA and protein expression of NMDAR1 was detected in pancreatic tissue. LO treatment caused acinar cell toxicity which was reversed by 250μM KYNA or SZR-72. Treatment of acini with NMDA (25, 250, 2000μM) did not influence the effects of KYNA or SZR-72. Moreover, SZR-72 reduced LO-induced H2O2 production of neutrophil granulocytes. KYNA and SZR-72 have dose-dependent protective effects on LOinduced AP or acinar toxicity which seem to be independent of pancreatic NMDA receptors. Furthermore, SZR-72 treatment suppressed AP-induced activation of neutrophil granulocytes. This study suggests that administration of KYNA and its derivative could be beneficial in AP.
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Reference:
Copper catalysis in organic synthesis – NCBI,
Special Issue “Fundamentals and Applications of Copper-Based Catalysts”