Disease relevance of N'-[5-(acetyl-hydroxy-amino)pentyl]-N-hydroxy-N-[5-[3-(hydroxy-methyl-carbamoyl)propanoylamino]pentyl]butanediamide

• Desferal without Mn had no effect on bone resorption by isolated osteoclasts [1].
• Desferal is a clinically approved iron chelator used to treat iron overload [2].
• In vitro studies confirmed that desferal inhibits breast tumor growth [2].
• However, pretreatment with the macrophage toxicant GdCl(3), the xanthine oxidase (XO) inhibitor allopurinol, and the Fe(III) chelator Desferal resulted in a marked decrease in free radical generation, lung inflammation, and lung injury [3].
• We examined the outer membrane proteins which appear during the growth of Neisseria gonorrhoeae F62 in complex medium supplemented with 25 microM Desferal mesylate, a potent iron chelator [4].

Psychiatry related information on N'-[5-(acetyl-hydroxy-amino)pentyl]-N-hydroxy-N-[5-[3-(hydroxy-methyl-carbamoyl)propanoylamino]pentyl]butanediamide

• Desferal also protected against 6-OHDA-induced deficit in locomotor activity, rearing, and exploratory behavior (sniffing) in a novel environment [5].
• These studies led us to develop novel brain-permeable iron chelators, the VK-28 series, with iron chelating and neuroprotective activity similar to desferal for ironing iron out from PD and other neurodegenerative diseases, such as Alzheimer's disease, Friedreich's ataxia, and Huntington's disease [5].
• Ultrafiltration experiments, using Amicon membranes with molecular weight exclusions of 1,000, 10,000 and 30,000 daltons, have revealed that Desferal, both in vitro and in vivo, markedly increases aluminum ultrafilterability in plasma from patients with dialysis dementia [6].

High impact information on N'-[5-(acetyl-hydroxy-amino)pentyl]-N-hydroxy-N-[5-[3-(hydroxy-methyl-carbamoyl)propanoylamino]pentyl]butanediamide

• When Desferal, an iron chelator, was added to these combinations, the four-drug combinations increased inhibition of cell growth and increased cytotoxicity [7].
• To prevent enzyme inhibition, erythrocyte membranes were treated with tBHP in the presence of 1 mmol/L ascorbate, a potential antioxidant, and 1 mmol/L desferal, an iron chelator [8].
• The antioxidant, desferal, also diminished increased mitochondrial Ca2+ after t-BuOOH and prevented cell death [9].
• H2O2-induced expression was prevented by catalase but unaffected by Desferal, indicating that metal catalyzed degradation of peroxide was not involved [10].
• From reported results we conclude that BPYTA is a powerful RR inhibitor (R2 subunit) which has a different mechanism of action from that of Desferal [11].

Chemical compound and disease context of N'-[5-(acetyl-hydroxy-amino)pentyl]-N-hydroxy-N-[5-[3-(hydroxy-methyl-carbamoyl)propanoylamino]pentyl]butanediamide

• Furthermore, desferal may have utility as an adjunctive chemotherapy due to its ability to inhibit breast tumor growth and cardiotoxic side effects without compromising the tumor-killing activity of an anthracycline chemotherapy drug [2].
• To test whether an iron-chelating antioxidant would interfere with the tumor-killing activity of doxorubicin, nude mice were transplanted with xenografts of human breast cancer MDA-MB 231 cells and then treated with doxorubicin and/or desferal [2].
• In this study, the effect of iron limitation was examined for the sexually transmitted infectious agent Chlamydia trachomatis in an in vitro model of human genital infection using the intracellular iron-chelating reagent deferoxamine mesylate (Desferal) [12].
• The ability of desferal (DFO) and of a new siderophore, desferrithiocin (DFT), to mobilize hepatic ferritin iron is observed in this model of iron overload [13].
• When desferal was allowed to accumulate intracellularly, no significant protection from homocysteine induced toxicity was observed [14].

Biological context of N'-[5-(acetyl-hydroxy-amino)pentyl]-N-hydroxy-N-[5-[3-(hydroxy-methyl-carbamoyl)propanoylamino]pentyl]butanediamide

• Desferal and hemin modulated iron-responsive element binding activity in HL-60 cells without affecting the phosphorylation state of IRP1 [15].
• The iron chelator desferal and the intracellular spin trap PBN caused a significant reduction in oxidative stress to almost control levels [16].
• The hydroxylation of salicylate was attenuated in mice treated with desferal while there was no effect of l-NAME compared with untreated mice [17].
• Three of the selected chelators (M30, HLA20 and M32) were the most effective in inhibiting iron-dependent lipid peroxidation in rat brain homogenates with IC50 values (12-16 microM), which is comparable with that of desferal, a prototype iron chelator that is not has orally active [18].
• The virulence of YeO3-R2 was determined in an orally infected desferal-attenuated murine model [19].

Anatomical context of N'-[5-(acetyl-hydroxy-amino)pentyl]-N-hydroxy-N-[5-[3-(hydroxy-methyl-carbamoyl)propanoylamino]pentyl]butanediamide

• In HL-60 cells, hemin (an iron source) stimulated m-Acon synthesis 3-fold after 4 h compared with cells treated with an iron chelator (Desferal) [20].
• In contrast to its effect on tumor cells, desferal did not inhibit growth of normal breast epithelial cells [2].
• Desferal (desferrioxamine)--a novel activator of connective tissue-type mast cells [21].
• Furthermore, the modulation of "basal" or "UVA-induced" level of LIP by either Desferal and/or hemin treatment significantly affected the extent of UVA-induced necrotic cell death and ATP depletion in all the cell lines [22].
• One- and two-electron reduction of quinone I led to calf thymus DNA-strand-break formation, a process that (a) was substantially decreased in experiments performed with dialysed DNA and in the presence of desferal and (b) was partially sensitive to superoxide dismutase and/or catalase [23].

Associations of N'-[5-(acetyl-hydroxy-amino)pentyl]-N-hydroxy-N-[5-[3-(hydroxy-methyl-carbamoyl)propanoylamino]pentyl]butanediamide with other chemical compounds

• The effect of Desferal (desferrioxamine), an iron-chelating agent with allergic side effects, was examined on human basophils and rodent mast cells (MCs) in vitro and in the human skin [21].
• Reversed siderophores as antimalarial agents. II. Selective scavenging of Fe(III) from parasitized erythrocytes by a fluorescent derivative of desferal [24].
• Finally, we summarize the effects of cerebroprotective pharmacological agents including the iron chelator desferal, superoxide dismutase, a stable radical from the nitroxide family, and HU-211, a nonpsychotoropic cannabinoid with antioxidant properties [25].
• In order to test the hypothesis that decreasing the vascular level of iron slows lesion growth, we examined the effects of the iron chelator Desferal (72 mg/kg/day, 5 days/week) on atherosclerosis and lesion iron content in cholesterol-fed New Zealand White rabbits [26].
• Treatment of intact liver and liver homogenate with sodium nitrite, or desferal, brings about the appearance of g = 2.03 and g = 4.3 electron paramagnetic resonance spectroscopy (EPR) signals, respectively [27].

Gene context of N'-[5-(acetyl-hydroxy-amino)pentyl]-N-hydroxy-N-[5-[3-(hydroxy-methyl-carbamoyl)propanoylamino]pentyl]butanediamide

• The cytostatic activity of desferal was partially ameliorated by pretreatment with iron-saturated transferrin, and transferrin receptor expression on breast cancer cells nearly doubled after exposure to desferal [2].
• The effects of adding iron, transferrin, or Desferal (an iron chelate) upon the growth of V. vulnificus in human and rabbit sera were also examined [28].
• The fact that the four-line spectrum obtained for the Abeta/PBN in PBS was completely abolished in the presence of the iron-chelating agent Desferal demonstrated the observed four-line spectrum to be iron-dependent [29].
• Further treatment with PIH or desferrioxamine (Desferal) increased the synthesis of TfR mRNA in induced Friend cells [30].
• Immuno-modulation of human lymphocyte function by desferroxamine (Desferal) [31].

Analytical, diagnostic and therapeutic context of N'-[5-(acetyl-hydroxy-amino)pentyl]-N-hydroxy-N-[5-[3-(hydroxy-methyl-carbamoyl)propanoylamino]pentyl]butanediamide

• In contrast, in all seven subjects studied, intradermal injection of Desferal (0.1 mg/ml to 100 mg/ml) elicited classic wheal-and-flare responses [21].
• Iron restriction caused a significant reduction in infectivity of C. trachomatis elementary bodies (EB) harvested from Desferal-exposed polarized epithelial cells when compared to that of EB harvested from iron-sufficient control cell cultures [12].
• Desferrithiocin stimulates ferritin iron mobilization, when administered either by gavage or by intraperitoneal injection, whereas desferal is active intraperitoneally but inactive orally [13].
• Using fast cyclic voltammetry, tyrosine hydroxylase (TH) immunohistochemistry, Perls' iron staining, and high-performance liquid chromatography-electrochemical detection, we measured the degeneration of dopaminergic neurons and increased iron content in the SN of rats overloaded with iron dextran and assessed the effects of treatment with Desferal [32].
• Pretreatment with dimethylthiourea (DMTU) or addition of desferal to the perfusate also significantly reduced the protein oxidation of lung ischemia/reperfusion [33].

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