1,720,964 research outputs found
Interaction of the potent antitumoral compounds Casiopeinas® with blood serum and cellular bioligands
No full textCasiopeinas® are among the few CuII compounds patented for their antitumor activity, but their mode of action has not been fully elucidated yet. One of them, Cas II-gly, is formed by 4,7-dimethyl-1,10-phenanthroline (Me2phen) and glycinato (Gly). In blood and cells, Cas II-gly can keep its identity or form mixed species with serum or cytosol bioligands (bL or cL) with composition CuII–Me2phen–bL/cL, CuII–Gly–bL/cL, or CuII–bL/cL. In this study, the binding of Cas II-gly with low molecular mass bioligands of blood serum (citric, L-lactic acid, and L-histidine) and cytosol (reduced glutathione (GSH), reduced nicotinamide adenine dinucleotide (NADH), adenosine triphosphate (ATP), and L-ascorbic acid) was examined through the application of instrumental (ElectroSpray Ionization-Mass Spectrometry and Electron Paramagnetic Resonance) and computational (Density Functional Theory) methods. The results indicated that mixed species CuII–Me2phen–bL/cL are formed, with the bioligands replacing glycinato. The formation of these adducts may participate in the copper transport toward the target organs and facilitate the cellular uptake or, in constrast, preclude it. In the systems with GSH, NADH and L-ascorbate, a redox reaction occurs with the partial oxidation of cL to the corresponding oxidized form (GSSG, NAD+ and dehydroascorbate) which interact with CuII. Formed CuI ion does not give complexation reactions with reduced or oxidized form of bioligands for its ‘soft’ character and low affinity for oxygen and nitrogen donors compared to CuII. However, CuI could promote Fenton-like reactions with production of reactive oxygen species (ROS) related to the antitumor activity of Casiopeinas®
Spectroscopic/Computational Characterization and the X-ray Structure of the Adduct of the VIVO-Picolinato Complex with RNase A
No full textThe structure, stability, and enzymatic activity of the adduct formed upon the reaction of the V-picolinato (pic) complex [VIVO(pic)2(H2O)], with an octahedral geometry and the water ligand in cis to the V=O group, with the bovine pancreatic ribonuclease (RNase A) were studied. While electrospray ionization-mass spectrometry, circular dichroism, and ultraviolet-visible absorption spectroscopy substantiate the interaction between the metal moiety and RNase A, electron paramagnetic resonance (EPR) allows us to determine that a carboxylate group, stemming from Asp or Glu residues, and imidazole nitrogen from His residues are involved in the V binding at acidic and physiological pH, respectively. Crystallographic data demonstrate that the VIVO(pic)2 moiety coordinates the side chain of Glu111 of RNase A, by substituting the equatorial water molecule at acidic pH. Computational methods confirm that Glu111 is the most affine residue and interacts favorably with the OC-6-23-Δenantiomer establishing an extended network of hydrogen bonds and van der Waals stabilizations. By increasing the pH around neutrality, with the deprotonation of histidine side chains, the binding of the V complex to His105 and His119 could occur, with that to His105 which should be preferred when compared to that to the catalytically important His119. The binding of the V compound affects the enzymatic activity of RNase A, but it does not alter its overall structure and stability
Behavior of the potential antitumor VIVO complexes formed by flavonoid ligands. 2. Characterization of sulfonate derivatives of quercetin and morin, interaction with the bioligands of the plasma and preliminary biotransformation studies
No full text- Abstract The biotransformation in the plasma and red blood cells of two potential antitumor VIVO complexes formed by flavonoid ligands (quercetin or que and morin or mor) and their sulfonic derivatives (quercetin-5′-sulfonic acid or queS and morin-5′-sulfonic acid or morS) was studied by spectroscopic (EPR, Electron Paramagnetic Resonance) and computational (DFT, Density Functional Theory) methods. Que and queS form with VIVO stable complexes, and in the systems with apo-transferrin (apo-hTf) and albumin (HSA) VO(que)2 and VO(queS)2 remain unchanged. VO(mor)2 and VO(morS)2 undergo displacement reactions to give the partial formation of (VO)x(HSA) and (VO)(apo-hTf)/(VO)2(apo-hTf); moreover, morS forms with apo-transferrin and albumin mixed species VO–morS–apo-hTf and VO–morS–HSA. In the systems with apo-hTf and HSA anisotropic EPR spectra at room temperature are detected in which the protein is not directly coordinated to VIVO2 + ion. This is explained assuming that the bis-chelated complexes interact strongly with the proteins through a network of hydrogen bonds with the polar groups present on the protein surface. It is suggested that this “indirect” transport of VIVO species could be common to all the species containing ligands which can interact with the blood proteins. Uptake experiments by red blood cells were also carried out, using vanadium concentration of 5.0 × 10− 4 M and incubation time in the range 0–160 min. VO(que)2/VO(queS)2 and VO(mor)2/VO(morS)2 cross the erythrocytes membrane and in the cytosol VO(que)2/VO(queS)2 do not transform, whereas VO(mor)2/VO(morS)2 give the partial formation of mixed species with hemoglobin (Hb) and other VIVO complexes
Biospeciation of Potential Vanadium Drugs of Acetylacetonate in the Presence of Proteins
No full textAmong vanadium compounds with potential medicinal applications, [VIVO(acac)2] is one of the most promising for its antidiabetic and anticancer activity. In the organism, however, interconversion of the oxidation state to +III and +V and binding to proteins are possible. In this report, the transformation of VIII(acac)3, VIVO(acac)2, and VVO2(acac) (Formula presented.) after the interaction with two model proteins, lysozyme (Lyz) and ubiquitin (Ub), was studied with ESI-MS (ElectroSpray Ionization-Mass Spectroscopy), EPR (Electron Paramagnetic Resonance), and computational (docking) techniques. It was shown that, in the metal concentration range close to that found in the organism (15–250 μM), VIII(acac)3 is oxidized to VIVO(acac)+ and VIVO(acac)2, which—in their turn—interact with proteins to give n[VIVO(acac)]–Protein and n[VIVO(acac)2]–Protein adducts. Similarly, the complex in the +IV oxidation state, VIVO(acac)2, dissociates to the mono-chelated species VIVO(acac)+ which binds to Lyz and Ub. Finally, VVO2(acac) (Formula presented.) undergoes complete dissociation to give the 'bare' VVO (Formula presented.) ion that forms adducts n[VVO2]–Protein with n = 1–3. Docking calculations allowed the prediction of the residues involved in the metal binding. The results suggest that only the VIVO complex of acetylacetonate survives in the presence of proteins and that its adducts could be the species responsible of the observed pharmacological activity, suggesting that in these systems VIVO2+ ion should be used in the design of potential vanadium drugs. If VIII or VVO2 potential active complexes had to be designed, the features of the organic ligand must be adequately modulated to obtain species with high redox and thermodynamic stability to prevent oxidation and dissociation
Effect of secondary interactions, steric hindrance and electric charge on the interaction of VIVO species with proteins
No full textThe interaction of two bis-chelated VIVO2+ species, formed by pipemidic (Hpip) and 8-hydroxyquinoline-5-sulphonic acids (H2hqs), with two small proteins, ubiquitin (Ub) and lysozyme (Lyz), was studied by EPR, ESI-MS, docking and DFT methods. The two complexes differ in electric charge (at neutral pH it is +2 and-2 for the species of Hpip and H2hqs, respectively), coordination geometry (cis-[VO(Hpip)2(H2O)]2+ is in equilibrium with the square pyramidal [VO(Hpip)2]2+, while cis-[VO(hqs)2(H2O)]2- is the only species in solution), and size (pipemidic acid is more sterically crowded than 8-hydroxyquinoline-5-sulphonic acid). The ESI-MS spectra showed that the number of cis-VO(hqs)22- moieties which interact with Ub is twice that of cis-VO(Hpip)22+ (adducts with formula n[VOL2]-Ub, where n = 1-4 for H2hqs and n = 1-2 for Hpip, were detected). The data can be rationalized in terms of the lower steric requirements of hqs2- and its negative charge, which favour secondary interactions with the surface groups of the protein. The EPR spectra revealed the coordination of Asp/Glu-COO or His-N donors, while docking calculations allowed us to identify the Ub residues involved in the VO(Hpip)2 (Asp39 and His68) and VO(hqs)2 binding (Glu18, Asp39, Asp58 and His68). The steric hindrance of Hpip is so important that the interaction of cis-[VO(Hpip)2(H2O)]2+ with lysozyme is completely prevented, while with cis-[VO(hqs)2(H2O)]2- the adducts n[VO(hqs)2]-Lyz (n = 1-2) were detected. Finally, the general effect of secondary interactions such as hydrogen bonds and van der Waals contacts, steric hindrance and electric charge on the V binding and stability of the adducts formed is also discussed, suggesting that these factors should be taken into account when designing new pharmacologically active compounds
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Behavior of the potential antitumor VIVO complexes formed by flavonoid ligands. 1. Coordination modes and geometry in solution and at the physiological pH
No full textThe coordination modes and geometry assumed in solution by the potent antitumor oxidovanadium(IV) complexes formed by different flavonoids were studied by spectroscopic (Electron Paramagnetic Resonance, EPR) and computational (Density Functional Theory, DFT) methods. A series of bidentate flavonoid ligands (L) with increasing structural complexity was examined, which can involve (CO, O−) donors and formation of five- and six-membered chelate rings, or (O−, O−) donors and five-membered chelate rings. The geometry corresponding to these coordination modes can be penta-coordinated, [VOL2], or cis-octahedral, cis-[VOL2(H2O)]. The results show that, at physiological pH, ligands provided with (CO, O−) donor set yield cis-octahedral species with “maltol-like” coordination when five-membered chelate rings are formed (as with 3-hydroxyflavone), while penta-coordinated structures with “acetylacetone-like” coordination are preferred when the chelate rings are six-membered (as with chrysin). When both the binding modes are possible, as with morin, the “acetylacetone-like” coordination is observed. For the ligands containing a catecholic donor set, such as 7,8-dihydroxyflavone, baicalein, fisetin, quercetin and rutin, the formation of square pyramidal complexes with (O−, O−) “catechol-like” coordination and five-membered chelate rings is preferred at physiological pH. The determination of the different coordination modes and geometry is important to define the biotransformation in the blood and the interaction of these complexes with the biological membranes
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