ABSTRACT
Herein, a series of 3-phenyliminoindolin-2-one derivatives were designed, synthesized, and screened for their antidepressant and anticonvulsant activities. The IR spectra of the compounds afforded NH stretching (3340-3346 cm(-1)) bands and C=O stretching (1731-1746 cm(-1)). In the (1)H-NMR spectra of the compounds, N-H protons of indoline ring were observed at 10.65-10.89 ppm generally as broad bands, and (13)C-NMR spectra of the compounds C=O were seen at 161.72-169.27 ppm. Interestingly, compounds 3o, 3p and 3r significantly shortened immobility time in the The forced swimming test (FST) and The tail suspension test (TST) at 50 mg/kg dose levels. In addition, compound 3r exhibited higher levels of efficacy than the reference standard fluoxetine but had no effect on locomotor activity in the open-field test. Compound 3r significantly increased serotonin and norepinephrine and the metabolite 5-hydroxyindoleacetic acid in mouse brain, suggesting that the effects of compound 3r may be mediated through these neurotransmitters. In the seizure screen, 15 compounds showed some degree against PTZ-induced seizure at a dose of 100 mg/kg, and the tested compounds did not show any neurotoxicity at a dose of 300 mg/kg in the rotarod test.
Subject(s)
Anticonvulsants/chemical synthesis , Anticonvulsants/pharmacology , Antidepressive Agents/chemical synthesis , Antidepressive Agents/pharmacology , Indoles/chemical synthesis , Indoles/pharmacology , Animals , Mice , Proton Magnetic Resonance Spectroscopy , Spectrometry, Mass, Electrospray IonizationABSTRACT
In this study, we investigated the tripolyphosphatase (TPPase) activity responsible for the hydrolysis of tripolyphosphates (TPP) in rabbit Psoas major muscle tissue. After a series of extraction and purification steps, myosin was identified to be a TPPase. Optimum pH and temperature for myosin-TPPase activity were 6.0 and 35°C, respectively. We also found that myosin-TPPase activity was significantly influenced by Mg(2+) and Ca(2+) levels, whose optimal concentrations were determined to be 3 and 6mM, respectively. Furthermore, myosin-TPPase was strongly inhibited by EDTA-4Na(+) and KIO(3), and was slightly activated by EDTA-2Na(+). These results suggest that it may be useful to regulate tripolyphosphate hydrolysis to enhance its function in meat processing.
Subject(s)
Acid Anhydride Hydrolases/chemistry , Acid Anhydride Hydrolases/isolation & purification , Muscle Proteins/isolation & purification , Myosins/chemistry , Psoas Muscles/enzymology , Animals , Calcium/metabolism , Diphosphates/metabolism , Electrophoresis, Polyacrylamide Gel , Enzyme Inhibitors/metabolism , Female , Hydrogen-Ion Concentration , Hydrolysis , Magnesium/metabolism , Muscle Proteins/chemistry , Myosins/isolation & purification , Polyphosphates/metabolism , Rabbits , TemperatureABSTRACT
Synphilin-1 represents a cytoplasmic protein that interacts with alpha-synuclein and localizes close to synaptic vesicles. The interaction of synphilin-1 with several proteins involved in Parkinson's disease suggests that it might be involved in the pathogenesis of the disease. Nonetheless, the function of synphilin-1 remains unclear. In the present study, we generated transgenic mice expressing human synphilin-1 under the prion protein promoter. Synphilin-1 was widely expressed in neurons in the brain including the substantia nigra, where massive loss of dopamine neurons was not observed. In the transgenic mouse brain, synphilin-1 protein was polyubiquitinated, and partially insoluble. Although modified-SHIRPA revealed no significant difference in behavior and morphology, the reduced rotarod performance and step length were observed in transgenic mice as compared with non-transgenic littermates. Synphilin-1 might be involved in motor function, and its accumulation in the central nervous system can cause motor impairments.
