Disease relevance of azetidine

• In cells infected with herpes simplex virus type 1 (HSV-1) in the presence of azetidine, synthesis of cellular proteins, including polypeptide C, was suppressed and infected cell polypeptides ICP 4, 0, 22 and 27 (apparent mol. wt. 170000, 120000, 75000 and 60000, respectively) were made [1].
• While each of the mutations (located within a conserved 26-amino-acid region of GK) was shown to confer AZ resistance (AZ(r)) on an L. monocytogenes proBA mutant, listerial transformants failed to exhibit the salt-tolerant phenotype observed in E. coli [2].
• A series of TEPA, Thio-TEPA, Seleno-TEPA, and azetidine analogs, including congeners containing an aminoxyl moiety, were synthesized and evaluated in vivo for anticancer activity against the murine lymphocytic leukemia P388 [3].
• 3. On the other hand, against five representative gram-positive bacteria, the relative mean antibacterial activity indices, GPM, remained high and rather constant regardless of structural variation in the azetidine moiety [4].
• Incubation of H35 hepatoma cells with 2.5 mM azetidine before or after treatments with X-rays causes a time- and sequence-dependent enhancement of cell killing [5].

High impact information on azetidine

• Upon exposure of cells to heat shock, the heavy metal cadmium, or the amino acid analogue azetidine, transcription at the hsp90alpha and hsp70 gene loci is strongly induced, and both hsp transcription sites become associated with speckles in >90% of the cells [6].
• Above a low basal activity of both HSFs, heat shock preferentially activates HSF1, whereas the amino acid analogue azetidine or the proteasome inhibitor MG132 coactivates both HSFs to different levels and hemin preferentially induces HSF2 [7].
• In support of this hypothesis, other treatments which act through different mechanisms to interfere with protein processing (i.e., tunicamycin, brefeldin A, and azetidine) were also found to be much more toxic for VHL-deficient cells [8].
• In cotransfection studies, YY1 specifically enhanced the transcriptional activation of the grp78 promoter under a variety of stress conditions: depletion of the endoplasmic reticulum calcium stores, protein glycosylation block, and formation of aberrant proteins by azetidine treatment [9].
• HSF activation in response to treatment with sodium arsenite or the proline analog azetidine was also depressed in hsp70-expressing cells relative to that in the nontransfected control cells [10].

Chemical compound and disease context of azetidine

• The alpha or immediate early mRNA of herpes simplex virus strain HSV-2(G) had a half-life of about 15 min if made in the absence of viral protein synthesis but was relatively stable if viral protein synthesis occurred, either freely or restricted by the presence of the proline analogue azetidine [11].
• The amino acid analog azetidine-2-carboxylic acid (azetidine) is a potent sensitizer to both hyperthermia and ionizing radiation [5].

Biological context of azetidine

• 7-azetidinylquinolones as antibacterial agents. 2. Synthesis and biological activity of 7-(2,3-disubstituted-1-azetidinyl)-4-oxoquinoline- and -1,8-naphthyridine-3-carboxylic acids. Properties and structure-activity relationships of quinolones with an azetidine moiety [12].
• We report in the present study that the induction of endogenous grp78 mRNA by the amino acid analogue azetidine (AzC) requires the integrity of a signal transduction pathway mediated by p38 mitogen-activated protein kinase (p38 MAPK) [13].
• Synthetic highlights include the construction of the azetidine ring using an intramolecular alkylation and the use of optically active alpha-methylbenzylamine as chiral auxiliary [14].
• Strong tetanus-induced long-term potentiation in the dentate gyrus of freely moving rats was not influenced by azetidine [15].
• In hippocampal slices, trans-azetidine-2,4-dicarboxylic acid also increased phosphoinositide hydrolysis, yet failed to show any effect on forskolin-stimulated formation of cyclic AMP, even if 1 mM azetidine was applied [15].

Anatomical context of azetidine

• The thermostability studies were capable of detecting altered G-6-PD in skin fibroblasts from a female heterozygous for a thermolabile mutant of G-6-PD, and in fibroblasts treated with a proline analogue, azetidine carboxylic acid [16].
• In Vero cells incubated at 40 degrees C or treated with azetidine at 37 degrees C, synthesis of a polypeptide ('C') of apparent mol. wt [1].
• Fasciola hepatica: azetidine inhibition of bile duct hyperplasia in the infected rat [17].
• Incorporation of azetidine carboxylate into hot trichloroacetic acid-insoluble material in sickle erythrocytes indicated that the homologue was present in the polypeptide backbone of the globin chains of sickle hemoglobin [18].
• In cultured mouse NIH 3T3 cells or human HeLa cells, Hsc70 mRNA levels are low under normal conditions, but can be induced 8-fold higher in both lines by treatment with the amino acid analog azetidine [19].

Associations of azetidine with other chemical compounds

• The influence on the structure-activity relationships of varying substituents in the azetidine ring and at position 8 (CH, CF, CCl, N) and N-1 (ethyl, fluoroethyl, cyclopropyl, tert-butyl, 4-fluorophenyl, and 2,4-difluorophenyl) was also studied [20].
• Synthesis and biological activities of angiotensin II, Sarilesin, and Sarmesin analogues containing Aze or Pip at position 7 [21].
• Structure reinvestigation of gelsemoxonine, a constituent of Gelsemium elegans, reveals a novel, azetidine-containing indole alkaloid [22].
• [structure: see text] The structure of gelsemoxonine, isolated from Gelsemium elegans Benth., was revised to be a novel oxindole alkaloid having an azetidine unit [22].
• New fluorinated pyrrolidine and azetidine amides as dipeptidyl peptidase IV inhibitors [23].

Gene context of azetidine

• All of the results from the functional studies of azetidine 10f are consistent with a selectivity of action at the NMDA receptor [24].
• The N-methanesulfonyl piperidine 23 and the N-trifluoroacetyl azetidine 26 were the most potent aggrecanase inhibitors both having an IC(50)=3nM while maintaining >100-fold selectivity over MMP-1, -2, and -9 [25].

References