Desferrioxamine (DFO) is a bacterial siderophore with a high affinity for iron, but low cell penetration. As part of our ongoing project focused on DFO-conjugates, we synthesized, purified, characterized and studied new mtDFOs (DFO conjugated to the Mitochondria Penetrating Peptides TAT49-57, 1A, SS02 and SS20) using a succinic linker. These new conjugates retained their strong iron binding ability and antioxidant capacity. They were relatively non toxic to A2780 cells (IC50 40–100 μM) and had good mitochondrial localization (Rr +0.45 –+0.68) as observed when labeled with carboxy-tetramethylrhodamine (TAMRA) In general, mtDFO caused only modest levels of mitochondrial DNA (mtDNA) damage. DFO-SS02 retained the antioxidant ability of the parent peptide, shown by the inhibition of mitochondrial superoxide formation. None of the compounds displayed cell cycle arrest or enhanced apoptosis. Taken together, these results indicate that mtDFO could be promising compounds for amelioration of the disease symptoms of iron overload in mitochondria.
Deferasirox (DFX), an orally active and clinically approved iron chelator, is being used extensively for the treatment of iron overload. However, its water insolubility makes it cumbersome for practical use. In addition to this, the low efficacy of DFX to remove brain iron prompted us to synthesize and evaluate a DFX-TAT(47-57) peptide conjugate for its iron chelation properties and permeability across RBE4 cell line, an in vitro model of the blood-brain barrier. The water-soluble conjugate was able to remove labile iron from buffered solution as well as from iron overloaded sera, and the permeability of DFX-TAT(47-57) conjugate into RBE4 cells was not affected compared to parent deferasirox. The iron bound conjugate was also able to translocate through the cell membrane.
Cell-impermeant iron chelator desferrioxamine (DFO) can have access to organelles if appended to suitable vectors. Mitochondria are important targets for the treatment of iron overload-related neurodegenerative diseases. Triphenylphosphonium (TPP) is a delocalized lipophilic cation used to ferry molecules to mitochondria. Here we report the synthesis and characterization of the conjugate TPP-DFO as a mitochondrial iron chelator. TPP-DFO maintained both a high affinity for iron and the antioxidant activity when compared to parent DFO. TPP-DFO was less toxic than TPP alone to A2780 cells (IC = 135.60 ± 1.08 and 4.34 ± 1.06 μmol L, respectively) and its native fluorescence was used to assess its mitochondrial localization (Rr = +0.56). These results suggest that TPP-DFO could be an interesting alternative for the treatment of mitochondrial iron overload e.g. in Friedreich's ataxia.
In this study, cellulose was obtained from the residues of pineapple crown by means of simple acid pretreatment and subsequent alkaline treatment. The pretreatment consisted of washing, drying, and chopping with high shear at pH = 5 under heating. The content of cellulose, hemicellulose, and lignin in the pineapple crown was determined by chemical methods. The cellulose obtained was compared with commercial cellulose by Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis, and X-ray diffraction (XDR). Thus, from the obtained fiber cellulose, a food container was prepared, and its physical-mechanical properties were determined. Then, after alkali treatment, the purity of cellulose was 84.7% from the pineapple crown (56.0%) and was compared with commercial cellulose (95%). FTIR results confirmed the removal of the non-cellulosic compounds after alkali treatment. The maximum pyrolysis temperature increased to 356 °C, higher than the original fiber (322 °C), indicating greater thermal stability after chemical treatment. Furthermore, the crystallinity increased to 68% with respect to the original fiber (27%). The physical properties of the container showed a decrease in the parameters in wet 95% RH, as expected, thus facilitating its reuse. These results indicate that the pineapple crown cellulose can be obtained with significant purity, from a single chemical treatment. In addition, this polymorphous cellulose can be used to make ecofriendly reusable food containers.
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