Glutamate, glutamine and glutamine synthetase in the neonatal rat brain following hypoxia

Exposing 7-day-old rat pups to hypoxia, 8% oxygen/92% nitrogen, for 3 h alters glutamate (GLU), glutamine and glutamine synthetase (GS) activity in the striatum, frontal cortex and hippocampus. Immediately following the hypoxic insult there is a rapid transient elevation of GLU followed by a fall and then recovery to control values within 6 h. Glutamine content initially decreased after the termination of the insult, rose thereafter and approached control values within 6 h. GS activity was depressed after hypoxia and gradually returned to normal levels within 6 h. GS mRNA was increased in the three brain regions studied after hypoxia and returned to control values within 24 h. These results suggest that hypoxia alters GLU metabolism in the immature brain.     

Synthesis of novel <Emphasis Type="Italic">N</Emphasis>-acyl-<Emphasis Type="Italic">β</Emphasis>-<Emphasis Type="SmallCaps">d</Emphasis>-glucopyranosylamines and ureas as potential lead cytostatic agents

Novel classes of acetylated and fully deprotected N-acyl-β-d-glucopyranosylamines and ureas have been synthesized and biologically evaluated. Acylation of the per-O-acetylated β-d-glucopyranosylurea (5), easily prepared via its corresponding phosphinimine derivative, by zinc chloride catalyzed reaction of the corresponding acyl chlorides RCOCl (a–f) gave the protected N-acyl-β-d-glucopyranosylureas (6a–f), in acceptable-to-moderate yields. Subsequent deacetylation of analogues 6a–f under Zemplén conditions afforded the fully deprotected derivatives 7a,b,d,e,f, while the desired urea 7c was formed after treatment of 6c with dibutyltin oxide. All protected and unprotected compounds were examined for their cytotoxic activity in different L1210, CEM and HeLa tumor cell lines and were also evaluated against a broad panel of DΝΑ and RNA viruses. Derivative 7c exhibited cytostatic activity against the three evaluated tumor cell lines (IC₅₀ 9–24 μΜ) and might be the basis for the synthesis of structure-related derivatives with improved cytostatic potential. Only analogue 6f weakly but significantly inhibited the replication of parainfluenza-3 virus, Sindbis virus and Coxsackie virus B4 in cell cultures at concentrations of 45–58 μM.