scholarly journals 4-Amino Bis-Pyridinium Derivatives as Novel Antileishmanial Agents

2014 ◽  
Vol 58 (7) ◽  
pp. 4103-4112 ◽  
Author(s):  
Verónica Gómez-Pérez ◽  
José Ignacio Manzano ◽  
Raquel García-Hernández ◽  
Santiago Castanys ◽  
Joaquín M. Campos Rosa ◽  
...  

ABSTRACTThe antileishmanial activity of a series of bis-pyridinium derivatives that are analogues of pentamidine have been investigated, and all compounds assayed were found to display activity against promastigotes and intracellular amastigotes ofLeishmania donovaniandLeishmania major, with 50% effective concentrations (EC50s) lower than 1 μM in most cases. The majority of compounds showed similar behavior in bothLeishmaniaspecies, being slightly more active againstL. majoramastigotes. However, compound VGP-106 {1,1′-(biphenyl-4,4′-diylmethylene)bis[4-(4-bromo-N-methylanilino)pyridinium] dibromide} exhibited significantly higher activity againstL. donovaniamastigotes (EC50, 0.86 ± 0.46 μM) with a lower toxicity in THP-1 cells (EC50, 206.54 ± 9.89 μM). As such, VGP-106 was chosen as a representative compound to further elucidate the mode of action of this family of inhibitors in promastigote forms ofL. donovani. We have determined that uptake of VGP-106 inLeishmaniais a temperature-independent process, suggesting that the compound crosses the parasite membrane by diffusion. Transmission electron microscopy analysis showed a severe mitochondrial swelling in parasites treated with compound VGP-106, which induces hyperpolarization of the mitochondrial membrane potential and a significant decrease of intracellular free ATP levels due to the inhibition of ATP synthesis. Additionally, we have confirmed that VGP-106 induces mitochondrial ROS production and an increase in intracellular Ca2+levels. All these molecular events can activate the apoptotic process inLeishmania; however, propidium iodide assays gave no indication of DNA fragmentation. These results underline the potency of compound VGP-106, which may represent a new avenue for the development of novel antileishmanial compounds.

2011 ◽  
Vol 77 (16) ◽  
pp. 5584-5590 ◽  
Author(s):  
Liang Shi ◽  
Sara M. Belchik ◽  
Andrew E. Plymale ◽  
Steve Heald ◽  
Alice C. Dohnalkova ◽  
...  

ABSTRACTShewanella oneidensisMR-1 possesses a periplasmic [NiFe]-hydrogenase (MR-1 [NiFe]-H2ase) that has been implicated in H2production and oxidation as well as technetium [Tc(VII)] reduction. To characterize the roles of MR-1 [NiFe]-H2ase in these proposed reactions, the genes encoding both subunits of MR-1 [NiFe]-H2ase were cloned and then expressed in an MR-1 mutant withouthyaBandhydAgenes. Expression of recombinant MR-1 [NiFe]-H2ase intransrestored the mutant's ability to produce H2at 37% of that for the wild type. Following purification, MR-1 [NiFe]-H2ase coupled H2oxidation to reduction of Tc(VII)O4−and methyl viologen. Change of the buffers used affected MR-1 [NiFe]-H2ase-mediated reduction of Tc(VII)O4−but not methyl viologen. Under the conditions tested, all Tc(VII)O4−used was reduced in Tris buffer, while in HEPES buffer, only 20% of Tc(VII)O4−was reduced. The reduced products were soluble in Tris buffer but insoluble in HEPES buffer. Transmission electron microscopy analysis revealed that Tc precipitates reduced in HEPES buffer were aggregates of crystallites with diameters of ∼5 nm. Measurements with X-ray absorption near-edge spectroscopy revealed that the reduction products were a mixture of Tc(IV) and Tc(V) in Tris buffer but only Tc(IV) in HEPES buffer. Measurements with extended X-ray adsorption fine structure showed that while the Tc bonding environment in Tris buffer could not be determined, the Tc(IV) product in HEPES buffer was very similar to Tc(IV)O2·nH2O, which was also the product of Tc(VII)O4−reduction by MR-1 cells. These results shows for the first time that MR-1 [NiFe]-H2ase catalyzes Tc(VII)O4−reduction directly by coupling to H2oxidation.


2011 ◽  
Vol 10 (01n02) ◽  
pp. 23-28
Author(s):  
RAVI BHATIA ◽  
V. PRASAD ◽  
M. REGHU

High-quality multiwall carbon nanotubes (MWNTs) were produced by a simple one-step technique. The production of MWNTs was based on thermal decomposition of the mixture of a liquid phase organic compound and ferrocene. High degree of alignment was noticed by scanning electron microscopy. The aspect ratio of as-synthesized MWNTs was quite high (more than 4500). Transmission electron microscopy analysis showed the presence of the catalytic iron nanorods at various lengths of MWNTs. Raman spectroscopy was used to know the quality of MWNTs. The ratio of intensity of the G-peak to the D-peak was very high which revealed high quality of MWNTs. Magnetotransport studies were carried out at low temperature and a negative MR was noticed.


Materials ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 1332
Author(s):  
Florian Riedlsperger ◽  
Bernadette Gsellmann ◽  
Erwin Povoden-Karadeniz ◽  
Oriana Tassa ◽  
Susanna Matera ◽  
...  

A thermokinetic computational framework for precipitate transformation simulations in Ta-containing martensitic Z-steels was developed, including Calphad thermodynamics, diffusion mobility data from the literature, and a kinetic parameter setup that considered precipitation sites, interfacial energies and dislocation density evolution. The thermodynamics of Ta-containing subsystems were assessed by atomic solubility data and enthalpies from the literature as well as from the experimental dissolution temperature of Ta-based Z-phase CrTaN obtained from differential scanning calorimetry. Accompanied by a comprehensive transmission electron microscopy analysis of the microstructure, thermokinetic precipitation simulations with a wide-ranging and well-documented set of input parameters were carried out in MatCalc for one sample alloy. A special focus was placed on modelling the transformation of MX into the Z-phase, which was driven by Cr diffusion. The simulation results showed excellent agreement with experimental data in regard to size, number density and chemical composition of the precipitates, showing the usability of the developed thermokinetic simulation framework.


Author(s):  
Hongyan Xu ◽  
Jing Guo ◽  
Qing Meng ◽  
Zhanling Xie

<i>Morchella</i> is a genus of edible fungi with strong resistance to Cd and the ability to accumulate it in the mycelium. However, the mechanisms conferring Cd resistance in <i>Morchella</i> are unknown. In the present study, morphological and physiological responses to Cd were evaluated in the mycelia of <i>Morchella spongiola</i>. Variations in hyphal micro-morphology including twisting, folding and kinking in mycelia exposed to different Cd concentrations (0.15, 0.9, 1.5, 2.4, 5.0 mg/L) were observed using scanning electron microscopy. Deposition of Cd precipitates on cell surfaces (at Cd concentrations > 2.4 mg/L) was shown by SEM-EDS. Transmission electron microscopy analysis of cells exposed to different concentrations of Cd revealed the loss of intracellular structures and the localization of Cd depositions inside/outside the cell. FTIR analysis showed that functional groups such as C=O, -OH, -NH and -CH could be responsible for Cd binding on the cell surface of <i>M. spongiola</i>. In addition, intracellular accumulation was observed in cultures at low Cd concentrations (< 0.9 mg/L), while extracellular adsorption occurred at higher concentrations. These results provide valuable information on the Cd tolerance mechanism in <i>M. spongiola</i> and constitute a robust foundation for further studies on fungal bioremediation strategies.


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