An efficient one-pot multicomponent reaction is reported for synthesizing a novel series 4-hydroxy-2-pyridone-fused spiropyran through the reaction of 4-hydroxy-6-methylpyridine-2-ones alkaloids, ...malononitrile or ethyl cyanoacetate, and ninhydrin or isatin derivatives. The optimized conditions for this reaction were obtained in ethanol solvent, acetic acid as catalyst, ambient temperature (for ninhydrin) or 70 °C (for isatin), and 8 hr reaction time. Mild and safe conditions, easy work-up and separation, high to excellent yields, and eco-compatibility are the main advantages of this synthesis for affording potentially bio-effective novel products.
A novel series of oxazolo4,5‐bpyridine‐2‐one based 1,2,3‐triazoles has been synthesized by click chemistry approach and evaluated for in vitro GSK‐3β inhibitory activity. Compound 4g showed maximum ...inhibition with IC50 value of 0.19 μm. Keeping in view the effect of GSK‐3β inhibition on inflammation, compounds 4g, 4d, 4f, 4i, 4n and 4q exhibiting significant GSK‐3β inhibition were examined for in vivo anti‐inflammatory activity in rat paw edema model. The compounds 4g, 4d, 4f and 4i showed pronounced in vivo anti‐inflammatory activity (76.36, 74.54, 72.72 and 70.90%, respectively, after 5h post‐carrageenan administration) and were further found to inhibit the pro‐inflammatory mediators, viz. NO, TNF‐α, IL‐1β, and IL‐6 substantially in comparison with indomethacin, an anti‐inflammatory drug as well as SB216763, a GSK‐3β inhibitor, reported to exert a similar effect. Histopathology studies confirmed the tolerance of gastric mucosa to these compounds.
We synthesized series of novel oxazolo4,5‐bpyridine‐2‐one based 1,2,3‐triazoles. Compounds were assessed for in vitro GSK‐3β inhibition and in vivo anti‐inflammatory activity. Compounds 4g, 4d, 4f and 4i were most active against both GSK‐3β and inflammation and also suppressed concentrations of NO, TNF‐α, IL‐1β and IL‐6 ex vivo. 4g, 4d, 4f and 4i also didn't cause any gastric ulceration and could be promising for GSK‐3β inhibition with potential for treatment of anti‐inflammatory disorders.
Abstract
An efficient synthesis of a novel series of 2‐pyridone‐pyrimidine derivatives via multicomponent reaction of different 4‐hydroxy‐6‐methylpyridine‐2‐ones, aromatic aldehydes, and barbituric ...acid or 6‐aminouracil in the presence of p‐toluene sulfonic acid in water has been reported. At first, the modified conditions to afford the best yield of a sample product were obtained (100 °C, one hour, and 100 mole % of p‐TSA) and then used for the others. The significant point of this report is to use Design‐Expert software for optimizing conditions. This reaction addition to having all the advantages of a green approach for synthesizing potentially bioactive compounds, such as eco‐compatibility, high yield of products, simple operation, and so, due to the using the methodic and pre‐calculated statistical optimization process, has high precision and accuracy. This approach can show a new path in optimizing the synthetic procedures of organic compounds.
Alzheimer's disease (AD), the most common form of progressive dementia in the elderly, is a chronic neurological disorder that decreases cognitive ability. Although the underlying cause of AD is yet ...unknown, oxidative stress and brain acetylcholine shortage are the key pathogenic causes.
The current study shows that these derivatives have the potential to improve memory in mice by inhibiting scopolamine-induced acetylcholinesterase activity, oxidative and nitrosative stress, and improving locomotor activity and muscle grip strength in the rota rod test. When compared to the illness control, the memory-enhancing potential of novel N-benzyl pyridine-2-one derivatives was highly significant (P < 0.0001).
The observed memory ameliorating effect of novel N-benzyl pyridine-2-one makes them as a a good choice for treatment of individuals with cognitive impairment.
An efficient multicomponent reaction was developed to synthesis of a novel series of (±)-7-methyl-4-aryl-4,6-dihydropyrido4,3-
d
pyrimidine-2,5(1
H
,3
H
)-dione/thione/imine from bio-based ...4-hydroxy-6-methylpyridine-2-ones, aromatic aldehydes and urea/thiourea/guanidine in the presence of ZnCl
2
.2H
2
O in ethanol at 70 °C. Mild conditions as well as the operational simplicity, easy work up, environmentally friendly are the most advantages of this multicomponent for synthesis of potentially bioactive new products.
Selective CB2 agonists have the potential for treating pain without central CB1-mediated adverse effects. Screening efforts identified 1,2-dihydro-3-isoquinolone 1; however, this compound has the ...drawbacks of being difficult to synthesize with two asymmetric carbons on an isoquinolone scaffold and of having a highly lipophilic physicochemical property. To address these two major problems, we designed the 2-pyridone-based lead 15a, which showed moderate affinity for CB2. Optimization of 15a led to identification of 39f with high affinity for CB2 and selectivity over CB1. Prediction of the binding mode of 39f in complex with an active-state CB2 homology model provided structural insights into its high affinity for CB2.
The CB2 receptor has emerged as a potential target for the treatment of pruritus as well as pain without CB1-mediated side effects. We previously identified 2-pyridone derivatives 1 and 2 as potent ...CB2 agonists; however, this series of compounds was found to have unacceptable pharmacokinetic profiles with no significant effect in vivo. To improve these profiles, we performed further structural optimization of 1 and 2, which led to the discovery of bicyclic 2-pyridone 18e with improved CB2 affinity and selectivity over CB1. In a mouse pruritus model, 18e inhibited compound 48/80 induced scratching behavior at a dose of 100mg/kg. In addition, the docking model of 18e with an active-state CB2 homology model indicated the structural basis of its high affinity and selectivity over CB1.
A new and efficient method for the demethylation of 6-membered aza-heterocyclic methyl ethers is described using lithium chloride and para-toluenesulfonic acid. This process is chemoselective for ...aza-heterocyclic methyl ethers in the presence of aryl methyl ethers.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A new cytotoxic compound, streptokordin, and four known compounds, nonactic acid, dilactone, trilactone, and nonactin, were isolated from the fermentation broth of a marine actinomycete strain ...collected in deep-sea sediments. Biochemical tests and 16S rDNA analysis indicated that the strain belongs to the genus Streptomyces. This actinomycete produces various bioactive secondary metabolites. Fractionations by solvent partitioning, silica vacuum flash chromatography, and reversed-phase HPLC gave a pure cytotoxic compound, designated streptokordin. Its structure was elucidated by FAB-MS, 1H, 13C, and 2D NMR spectroscopy. Streptokordin exhibited significant cytotoxicity against seven human cancer cell lines but showed no growth inhibition against various microorganisms including bacteria and fungi.
Hypusine synthesis in the eukaryotic initiation factor 5A is a unique two-step posttranslational modification. After deoxyhypusine is generated by the deoxyhypusine synthase, the deoxyhypusine ...hydroxylase (EC 1.14.99.29) catalyzes the formation of mature hypusine. A rapid assay for monitoring the deoxyhypusine hydroxylase activity was established, employing the oxidative cleavage of the hypusyl residue and subsequent extraction of the generated aldehydes. As metal ion chelators have been reported to inhibit the deoxyhypusine hydroxylase, the mechanism of this inhibition and the effect of transition metal ions on the enzyme activity were investigated. A ferric ion appears to be essential for enzymatic activity, the inhibition of which is entirely attributed to the metal ion bunding capacity of the chelators.
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