Parkinson’s disease is a neurodegenerative disorder associated with oxidative stress and glutathione depletion. The induction of cellular glutathione levels by exogenous molecules is a promising neuroprotective approach to limit the oxidative damage that characterizes Parkinson’s disease pathophysiology. Dithiolethiones, a class of sulfur-containing heterocyclic molecules, are known to increase cellular levels of glutathione; however, limited information is available regarding the influence of dithiolethione structure on activity. Herein, we report the design, synthesis, and pharmacological evaluation of a further series of dithiolethiones in the SH-SY5Y neuroblastoma cell line.
Results
Our structure–activity relationships data show that dithiolethione electronic properties, given as Hammett σp constants, influence glutathione induction activity and compound toxicity. The most active glutathione inducer identified, 6a, dose-dependently protected cells from 6-hydroxydopamine toxicity. Furthermore, the protective effects of 6a were abrogated by the inhibitor of glutathione synthesis, buthionine sulfoximine, confirming the importance of glutathione in the protective activities of 6a.
Conclusions
The results of this study further delineate the relationship between dithiolethione chemical structure and glutathione induction. The neuroprotective properties of analog 6a suggest a role for dithiolethiones as potential antiparkinsonian agents.
We investigate the properties of persistent charge current driven by magnetic flux in aquasi-periodic mesoscopic Fibonacci ring with Rashba and Dresselhaus spin-orbitinteractions. Within a tight-binding framework we work out individual state currentstogether with net current based on second-quantized approach. A significant enhancement ofcurrent is observed in presence of spin-orbit coupling and sometimes it becomes orders ofmagnitude higher compared to the spin-orbit interaction free Fibonacci ring. We alsoestablish a scaling relation of persistent current with ring size, associated with theFibonacci generation, from which one can directly estimate current for any arbitrary flux,even in presence of spin-orbit interaction, without doing numerical simulation. Thepresent analysis indeed gives a unique opportunity of determining persistent current andhas not been discussed so far. 相似文献
We have developed a novel class of synthetic molecular transporters that contain eight residues of guanidine with an inositol dimer as the scaffold. The dimers were prepared by connecting two units of myo- or scyllo-inositol via a carbonate or amide linkage, and the multiple units of the guanidine functionality were constructed on the inositol scaffold by means of peracylation with omega-aminocarboxylate derivatives of varying length. Bioassays based on confocal laser scanning microscopy and fluorescence-activated cell sorter analyses indicated that these transporters display a varying degree of membrane translocating ability, and the intracellular localization and mouse-tissue distribution studies strongly suggested that these transporters undergo substantially different mechanistic processes from those of peptide transporters reported to date. It was also shown that doxorubicin, an anticancer antibiotic, can be efficiently delivered into mouse brain by aid of this type of transporter. 相似文献
Interaction of the bile salts, sodium cholate and sodium deoxy cholate with albumin has been probed by fluorescence and circular dichroism studies. Both covalently and non-covalently labeled protein have been used to follow the aggregation of bile salts in presence of protein and to study bile salt-protein interactions in general. Time resolved studies, in agreement with steady-state fluorescence and circular dichroism studies, indicate alteration of protein secondary structure due to positive co-operative effects in bile salt binding to protein. These studies also indicate that covalent labeling may not always be good for studying proteins as it causes alteration of protein secondary structure. 相似文献
The optoelectronic and structural properties of p-type a-SiOx:H films have been studied. The deposition parameters e.g. chamber pressure and diborane to silane ratio are optimized to get a film with dark conductivity (σd) 7.9×10−6 S cm−1 and photoconductivity 9.3×10−6 S cm−1 for an optical gap (E04) of 1.94 eV. The decrease of optical gap accompanied by the increase of conductivity is due to less oxygen incorporation in the film, which is substantiated by the decrease of the intensity of SiO absorption spectra. The properties are very much effected by the chamber pressure and diborane to silane ratio. 相似文献
The requirement of getting continuous electricity at low cost is essential but challenging. Especially in the undeveloped countries there is no sufficient electricity for the people to do their daily regular works. In order to overcome this problem different renewable energy sources are sought and being explored. One of the approaches is to have a cooking system that is energized from the solar power, not directly using a solar cooker but by storing the energy in the form of heat that can be utilized as per requirement. This paper reports the design and fabrication of an alternative system to generate heat using solar radiation. This chulha is helpful in effective heating with the help of solar radiations at lower costs. A cooking technology is presented consisting of a solar panel directly connected to an electric heater inside of a well-insulated chamber. An insulated container with fixed amount of oil is heated up. The heat is found to be retained in the chamber even after sun set which is sufficient for heating water for making tea. The possible causes of temperature drop and possible remedy has been pointed out and discussed in this paper. 相似文献
Iron plays a vital role in several cellular functions due to its unique physiochemical properties. Iron concentration increases in the brain with age due to multiple factors. Excessive amount of iron can lead to formation of reactive oxygen species. Neurodegenerative disorders are characterized by iron supplemented increase in oxidative stress and cellular damage. There is an urgent need of novel therapies which should not only provide symptomatic relief but also be able to modulate iron accumulation in the brain. Therefore, the development of novel iron chelators as neuroprotective agents for the treatment of neurodegeneration is an emerging trend. Several iron chelators including 8-hydroxyquinoline derivatives, dopaminergic agonists and natural products are under preclinical and clinical investigations for the treatment of neurodegenerative disorders.
A highly efficient photonic crystal dual band wavelength demultiplexer (DBWD) using silicon-on-insulator (SOI) substrates is proposed for demultiplexing two optical communication wavelengths, 1.31 μm and 1.55 μm. Demultiplexing of two wavelength channels is obtained by modifying the propagation properties of guided modes in two arms of Y type photonic crystal structure. Propagation characteristics of proposed DBWD are analyzed utilizing 3D finite difference time domain (FDTD) method. Enhancement in spectral response is further obtained by optimizing the Y junction of demultiplexer giving rise to high transmission and extinction ratio for the wavelengths, 1.31 μm and 1.55 μm. Hence it validates the efficiency of proposed optimized DBWD design for separating two optical communication wavelengths, 1.31 μm and 1.55 μm. Tolerance analysis was also performed to check the effect of variation of air hole radius, etch depth and refractive index on the transmission characteristics of the proposed design of SOI based photonic crystal DBWD. 相似文献