Iron complexes
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The complexes of Fe(II), Mn(II) and Ni(II) with a combination of a Schiff base, nitrogen-donor ligand or macrocyclic ligand and trithiocyanuric acid (ttcH3) were prepared and characterized by elemental analysis and spectroscopies. Crystal and molecular structures of the iron complex of composition [Fe(L1)](ttcH2)(ClO4)·EtOH·H2O (1), where L1 is Schiff base derived from tris(2-aminoethyl)amine and 2-pyridinecarboxaldehyde, were solved. It was found that the Schiff base is coordinated to the central iron atom by six nitrogens forming deformed octahedral arrangement, whereas trithiocyanurate(1-) anion, perchlorate and solvent molecules are not coordinated. The X-ray structure of the Schiff base sodium salt is also presented and compared with the iron complex. The anticholinesterase activity of the complexes was also studied.
- MeSH
- cholinesterasové inhibitory chemická syntéza chemie farmakologie MeSH
- cholinesterasy metabolismus MeSH
- enzymatické testy MeSH
- ethylendiaminy chemie MeSH
- komplexní sloučeniny chemická syntéza chemie farmakologie MeSH
- komplexní směsi chemie MeSH
- krysa rodu rattus MeSH
- krystalografie rentgenová MeSH
- ligandy MeSH
- mangan chemie MeSH
- mozek účinky léků enzymologie MeSH
- nikl chemie MeSH
- pyridiny chemie MeSH
- Schiffovy báze chemie MeSH
- triaziny chemie MeSH
- železo chemie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Flavonoids are common plant natural products able to suppress ROS-related damage and alleviate oxidative stress. One of key mechanisms, involved in this phenomenon is chelation of transition metal ions. From a physiological perspective, iron is the most significant transition metal, because of its abundance in living organisms and ubiquitous involvement in redox processes. The chemical, pharmaceutical, and biological properties of flavonoids can be significantly affected by their interaction with transition metal ions, mainly iron. In this review, we explain the interaction of various flavonoid structures with Fe(II) and Fe(III) ions and critically discuss the influence of chelated ions on the flavonoid biochemical properties. In addition, specific biological effects of their iron metallocomplexes, such as the inhibition of iron-containing enzymes, have been included in this review.
- MeSH
- antioxidancia chemie farmakologie MeSH
- chelátory chemie farmakologie MeSH
- flavonoidy chemie MeSH
- hem chemie MeSH
- ionty chemie metabolismus MeSH
- komplexní sloučeniny chemie MeSH
- lidé MeSH
- molekulární struktura MeSH
- vazba proteinů MeSH
- vztahy mezi strukturou a aktivitou MeSH
- železo chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Ateroskleróza zůstává stále vedoucí příčinou úmrtí. Jedná se o komplexní inflamatorní proces charakteru fibroproduktivního „reparačního“ zánětu, který se odehrává v arteriální stěně. Na souboru těchto dějů se podílí zejména monocyty/makrofágy, B i T lymfocyty, endotelie a buňky hladké svaloviny. Článek popisuje úlohu železa v jednotlivých krocích patogeneze aterosklerózy, druhá část poukazuje na různé klinické studie, které se zabývaly asociací mezi výskytem kardiovaskulární onemocnění a železem.
Atherosclerosis remains the leading cause of death. It is a complex fibroproductive "reparative" inflammatory process, which takes place in the arterial wall. The set of these processes is mainly caused by monocytes/macrophages, B and T lymphocytes, endothelial cells and smooth muscle cells. The article describes the role of iron in individual steps of the pathogenesis of atherosclerosis, the second part summarises various clinical studies investigating the association between iron and the occurrence of cardiovascular diseases.
MAIN CONCLUSION: Fe uptake machinery of chloroplasts prefers to utilise Fe(III)-citrate over Fe-nicotianamine complexes. Iron uptake in chloroplasts is a process of prime importance. Although a few members of their iron transport machinery were identified, the substrate preference of the system is still unknown. Intact chloroplasts of oilseed rape (Brassica napus) were purified and subjected to iron uptake studies using natural and artificial iron complexes. Fe-nicotianamine (NA) complexes were characterised by 5 K, 5 T Mössbauer spectrometry. Expression of components of the chloroplast Fe uptake machinery was also studied. Fe(III)-NA contained a minor paramagnetic Fe(II) component (ca. 9%), a paramagnetic Fe(III) component exhibiting dimeric or oligomeric structure (ca. 20%), and a Fe(III) complex, likely being a monomeric structure, which undergoes slow electronic relaxation at 5 K (ca. 61%). Fe(II)-NA contained more than one similar chemical Fe(II) environment with no sign of Fe(III) components. Chloroplasts preferred Fe(III)-citrate compared to Fe(III)-NA and Fe(II)-NA, but also to Fe(III)-EDTA and Fe(III)-o,o'EDDHA, and the Km value was lower for Fe(III)-citrate than for the Fe-NA complexes. Only the uptake of Fe(III)-citrate was light-dependent. Regarding the components of the chloroplast Fe uptake system, only genes of the reduction-based Fe uptake system showed high expression. Chloroplasts more effectively utilize Fe(III)-citrate, but hardly Fe-NA complexes in Fe uptake.
- MeSH
- Brassica napus metabolismus MeSH
- chloroplasty metabolismus MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- kyselina azetidinkarboxylová analogy a deriváty metabolismus MeSH
- spektroskopie Mossbauerova MeSH
- transkriptom MeSH
- železité sloučeniny metabolismus MeSH
- železo metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Every eukaryote requires iron, which is also true for the parasitic protist Trypanosoma brucei, the causative agent of sleeping sickness in humans and nagana in cattle. T. brucei undergoes a complex life cycle during which its single mitochondrion is subject to major metabolic and morphological changes. SCOPE OF REVIEW: This review covers what is known about processes associated with iron-sulfur clusters and heme metabolism in T. brucei. We discuss strategies by which iron and heme are acquired and utilized by this model parasite, emphasizing the differences between its two life cycle stages residing in the bloodstream of the mammalian host and gut of the insect vector. Finally, the role of iron in the host-parasite interactions is discussed along with their possible exploitation in fighting these deadly parasites. MAJOR CONCLUSIONS: The processes associated with acquisition and utilization of iron, distinct in the two life stages of T. brucei, are fine tuned for the dramatically different host environment occupied by them. Although the composition and compartmentalization of the iron-sulfur cluster assembly seem to be conserved, some unique features of the iron acquisition strategies may be exploited for medical interventions against these parasites. GENERAL SIGNIFICANCE: As early-branching protists, trypanosomes and related flagellates are known to harbor an array of unique features, with the acquisition of iron being another peculiarity. Thanks to intense research within the last decade, understanding of iron-sulfur cluster assembly and iron metabolism in T. brucei is among the most advanced of all eukaryotes.
Elevated catecholamine levels are known to induce damage of the cardiac tissue. This catecholamine cardiotoxicity may stem from their ability to undergo oxidative conversion to aminochromes and concomitant production of reactive oxygen species (ROS), which damage cardiomyocytes via the iron-catalyzed Fenton-type reaction. This suggests the possibility of cardioprotection by iron chelation. Our in vitro experiments have demonstrated a spontaneous decrease in the concentration of the catecholamines epinephrine and isoprenaline during their 24-h preincubation in buffered solution as well as their gradual conversion to oxidation products. These changes were significantly augmented by addition of iron ions and reduced by the iron-chelating agent salicylaldehyde isonicotinoyl hydrazone (SIH). Oxidized catecholamines were shown to form complexes with iron that had significant redox activity, which could be suppressed by SIH. Experiments using the H9c2 cardiomyoblast cell line revealed higher cytotoxicity of oxidized catecholamines than of the parent compounds, apparently through the induction of caspase-independent cell death, whereas co-incubation of cells with SIH was able to significantly preserve cell viability. A significant increase in intracellular ROS formation was observed after the incubation of cells with catecholamine oxidation products; this could be significantly reduced by SIH. In contrast, parent catecholamines did not increase, but rather decreased, cellular ROS production. Hence, our results demonstrate an important role for redox-active iron in catecholamine autoxidation and subsequent toxicity. The iron chelator SIH has shown considerable potential to protect cardiac cells by both inhibition of deleterious catecholamine oxidation to reactive intermediates and prevention of ROS-mediated cardiotoxicity.
- MeSH
- aldehydy farmakologie MeSH
- buněčné linie MeSH
- chelátory železa farmakologie MeSH
- cytoprotekce MeSH
- enzymatické testy MeSH
- hydrazony farmakologie MeSH
- kaspasy metabolismus MeSH
- katecholaminy metabolismus MeSH
- kompetitivní vazba MeSH
- komplexní sloučeniny farmakologie MeSH
- krysa rodu rattus MeSH
- kyselina askorbová chemie MeSH
- myoblasty srdeční cytologie účinky léků metabolismus MeSH
- oxidace-redukce MeSH
- oxidační stres MeSH
- reaktivní formy kyslíku metabolismus MeSH
- viabilita buněk účinky léků MeSH
- železo metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The content of nitrite admixture in preparations of dinitrosyl iron complexes (DNIC) with glutathione synthesized by treatment of aqueous solutions of Fe2+ + glutathione with gaseous NO (complex 1) or by mixing solutions of S-nitrosoglutathione (GS-NO) with solutions of Fe2+ + glutathione (complex 2) was determined using the Griess method and HPLC as well as from the level of HNO2 formed upon interaction of gaseous NO with acidified distilled water. In both preparations, DNIC were predominantly represented by the binuclear form (B-DNIC). In complex 1, the appearance of nitrite in DNIC solutions was induced by nitrogen dioxide present in gaseous NO; its interaction with NO gives an adduct, which is further hydrolyzed to nitrite in aqueous solutions. In complex 2, the presence of nitrite admixture could appear in the presence of nitrite non-incorporated into GS-NO synthesized by mixing glutathione and nitrite in acid media. The per cent content of nitrite (with respect to the total content of complex 1) was 6%, whereas in complex 2 it was as low as 0.4%. Such a low level of nitrite contamination in the course of conventional synthesis of DNIC with glutathione does not make any significant contribution to their biomedical (e.g., hypotensive or vasodilator) activity.
- MeSH
- antihypertenziva * farmakologie MeSH
- dusičnany farmakologie MeSH
- farmaceutická chemie metody přístrojové vybavení MeSH
- kontaminace léku * MeSH
- lidé MeSH
- oxidy dusíku farmakologie MeSH
- S-nitrosoglutathion farmakologie MeSH
- sloučeniny dusíku * farmakologie MeSH
- spektrofotometrie metody přístrojové vybavení využití MeSH
- statistika jako téma MeSH
- vazodilatancia farmakologie MeSH
- vysokoúčinná kapalinová chromatografie metody přístrojové vybavení využití MeSH
- železo farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Alternaria alternata is a common fungus strongly related with severe allergic asthma, with 80% of affected individuals being sensitized solely to its major allergen Alt a 1. Here, we assessed the function of Alt a 1 as an innate defense protein binding to micronutrients, such as iron-quercetin complexes (FeQ2), and its impact on antigen presentation in vitro. Binding of Alt a 1 to FeQ2 was determined in docking calculations. Recombinant Alt a 1 was generated, and binding ability, as well as secondary and quaternary structure, assessed by UV-VIS, CD, and DLS spectroscopy. Proteolytic functions were determined by casein and gelatine zymography. Uptake of empty apo- or ligand-filled holoAlt a 1 were assessed in human monocytic THP1 cells under the presence of dynamin and clathrin-inhibitors, activation of the Arylhydrocarbon receptor (AhR) using the human reporter cellline AZ-AHR. Human PBMCs were stimulated and assessed for phenotypic changes in monocytes by flow cytometry. Alt a 1 bound strongly to FeQ2 as a tetramer with calculated Kd values reaching pico-molar levels and surpassing affinities to quercetin alone by a factor of 5000 for the tetramer. apoAlt a 1 but not holoAlta 1 showed low enzymatic activity against casein as a hexamer and gelatin as a trimer. Uptake of apo- and holo-Alt a 1 occurred partly clathrin-dependent, with apoAlt a 1 decreasing labile iron in THP1 cells and holoAlt a 1 facilitating quercetin-dependent AhR activation. In human PBMCs uptake of holoAlt a 1 but not apoAlt a 1 significantly decreased the surface expression of the costimulatory CD86, but also of HLADR, thereby reducing effective antigen presentation. We show here for the first time that the presence of nutritional iron complexes, such as FeQ2, significantly alters the function of Alt a 1 and dampens the human immune response, thereby supporting the notion that Alt a 1 only becomes immunogenic under nutritional deprivation.
- MeSH
- alergeny * MeSH
- Alternaria metabolismus MeSH
- bronchiální astma * MeSH
- kaseiny MeSH
- klathrin MeSH
- lidé MeSH
- quercetin MeSH
- železo metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
