Synthesis of Sulfur‐Substituted Quinolizidines and Pyrido[1,2‐a]azepines by Ring‐Closing Metathesis.

Chou, Shang‐Shing P.; Liang, Chu‐Fang; Lee, Tse-Ming; Liu, Chih-Fen

doi:10.1002/chin.200749159

Cited by 3 publications

(5 citation statements)

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“…In that case, the combined molecules might not achieve their individual dose effectiveness inside cells to scavenge free radicals. The fact that folic acid and NSC47 have similar bicyclic ring structures [ 21 , 24 , 25 ] suggests that interactions between these two bioactive molecules for cellular uptake may be possible. On the other hand, the current cytoprotective dose of folic acid supplement (100 μM) was not effective in intracellular superoxide scavenging, which may provide an alternative explanation of why the combined molecules did not have a synergistic effect on superoxide levels of Aβ-treated microglial cells.…”

Section: Discussionmentioning

confidence: 99%

“…NSCs were prepared and characterized according to the method of Chou et al [ 24 , 25 ]. The NSCs were dissolved in dimethyl sulfoxide (DMSO) to a concentration of 100 mM and then stored at 4 ºC.…”

Section: Methodsmentioning

confidence: 99%

“…NSC47 belongs to a less-common framework of pyridoazepines, but some pyridoazepines were found to have very strong insecticidal activities [ 21 ], and were studied as potential dopamine D1 receptors [ 22 ] and nicotinic acetylcholinergic receptor ligands [ 23 ]. Synthesis methods for structures like NSC42, -43, and -47 were previously reported by our lab [ 24 , 25 ]. Although a few functional properties of NSC42, -43, and -47 were reported, it remains unclear if such bioactive NSCs possess any antioxidant activity to protect against Aβ-induced cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

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The Isolated and Combined Effects of Folic Acid and Synthetic Bioactive Compounds against Aβ(25-35)-Induced Toxicity in Human Microglial Cells

et al. 2010

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Folic acid plays an important role in neuronal development. A series of newly synthesized bioactive compounds (NSCs) was reported to exhibit immunoactive and neuroprotective functions. The isolated and combined effects of folic acid and NSCs against β-amyloid (Aβ)-induced cytotoxicity are poorly understood. These effects were tested using human microglia cells (C13NJ) subjected to Aβ(25-35) challenge. According to an MTT assay, treatment of C13NJ cells with Aβ(25-35) at 10~100 μM for 48 h induced 18%~43% cellular death in a dose-dependent manner (p < 0.05). Aβ(25-35) treatment at 25 μM induced nitrite oxide (NO) release, elevated superoxide production, and reduced the distribution of cells in the S phase. Preincubation of C13NJ with 100 μM folic acid protected against Aβ(25-35)-induced cell death, which coincided with a reduction in NO release by folic acid supplements. NSC47 at a level of 50 μM protected against Aβ(25-35)-induced cell death and reduced Aβ-promoted superoxide production (p < 0.05). Folic acid in combination with NSC47 at their cytoprotective doses did not synergistically ameliorate Aβ(25-35)-associated NO release, superoxide production, or cell cycle arrest. Taken together, folic acid or NSC treatment alone, but not the combined regimen, protected against Aβ(25-35)-induced cell death, which may partially, if not completely, be mediated by free radical-scavenging effects.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Isolated and Combined Effects of Folic Acid and Synthetic Bioactive Compounds against Aβ(25-35)-Induced Toxicity in Human Microglial Cells

et al. 2010

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“…A series of quinolizinone and pyridone relative compounds (FJU-C1 to C7) were synthesized, as shown in Fig. 1A [11] , [12] , [13] , [14] , [15] and their name of these chemical compounds were listed on Table 1 . Lipopolysaccharides (LPS, Escherichia Coli 0111:B4) were purchased from Sigma-Aldrich (Saint Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

FJU-C4, a New 2-Pyridone Compound, Attenuates Lipopolysaccharide-Induced Systemic Inflammation via p38MAPK and NF-κB in Mice

et al. 2013

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Despite advances in antibiotic therapy and intensive care, the mortality caused by systemic inflammatory response syndrome and severe sepsis remains high. The use of anti-inflammatory agents to attenuate inflammatory response during acute systemic inflammatory reactions may improve survival rates. Here we show that a newly synthesized 2-pyridone compound (FJU-C4) can suppress the expression of late inflammatory mediators such as iNOS and COX-2 in murine macrophages. The pro-inflammatory cytokines, including TNFα, IL-1β, and IL-6, were dose-dependently suppressed by FJU-C4 both in mRNA and protein levels. In addition, the expression of TNFα was inhibited from as early as 2 hours after exposure to LPS stimulation. The production of mature pro-inflammatory cytokines was also suppressed by pretreatment with FJU-C4 in either cell culture medium or mice serum when stimulated by LPS. FJU-C4 prolongs mouse survival and prevents mouse death from LPS-induced systemic inflammation when the dose of FJU-C4 is over 5 mg/kg. The activities of ERK, JNK, and p38MAPK were induced by LPS stimulation on murine macrophage cell line, but only p38MAPK signaling was dramatically suppressed by pretreatment with the FJU-C4 compound in a dose-dependent manner. NF-κB activation also was suppressed by FJU-C4 compound. These findings suggest that the FJU-C4 compound may act as a promising therapeutic agent against inflammatory diseases by inhibiting the p38MAPK and NF-κB signaling pathway.

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“…Imino-Diels-Alder reactions are very useful for the synthesis of tetrahydropyridines [17][18][19]. We have previously developed a new imino-Diels-Alder reaction of thio-substituted 3-sulfolenes with p-toluenesulfonyl isocyanate (PTSI) to synthesize piperidine derivatives [20,21], and have used this method to prepare some indolizidines and quinolizidines [22][23][24][25][26][27][28][29][30][31][32]. We have recently reported the use of cross metathesis (CM) to transform the terminal alkenes 1a-c into the α,β-unsaturated esters 2a-c, and after detosylation the resulting amides 3a-c…”

Section: Introductionmentioning

confidence: 99%

Studies toward the First Stereoselective Total Synthesis of (±)-Quinolizidine 195C and Other Transformations

Chou

Huang

2013

Molecules

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Abstract:Starting from a thio-substituted 4-quinolizidinone, a series of C-6 alkylated derivatives with a trans C-6, C-9a relationship was synthesized. Further transformations led to the first stereoselective total synthesis of the structure proposed for (±)-quinolizidine 195C, the major alkaloid isolated from the skin extracts of the Madagascan frog Mantella betsileo. Since the spectral data of the synthetic and natural products differed significantly, the true structure of (±)-quinolizidine 195C remains uncertain.

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Synthesis of Sulfur‐Substituted Quinolizidines and Pyrido[1,2‐a]azepines by Ring‐Closing Metathesis.

Cited by 3 publications

References 1 publication

The Isolated and Combined Effects of Folic Acid and Synthetic Bioactive Compounds against Aβ(25-35)-Induced Toxicity in Human Microglial Cells

The Isolated and Combined Effects of Folic Acid and Synthetic Bioactive Compounds against Aβ(25-35)-Induced Toxicity in Human Microglial Cells

FJU-C4, a New 2-Pyridone Compound, Attenuates Lipopolysaccharide-Induced Systemic Inflammation via p38MAPK and NF-κB in Mice

Studies toward the First Stereoselective Total Synthesis of (±)-Quinolizidine 195C and Other Transformations

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