Double-strand DNA cleavage induced by oxindole-Schiff base copper(II) complexes with potential antitumor activity

Some oxindole-Schiff base copper(II) complexes have already shown potential antitumor activity towards different cells, inducing apoptosis in a process modulated by the ligand, and having nuclei and mitochondria as main targets. Here, three novel copper(II) complexes with analogous ligands were isolated and characterized by spectroscopic techniques, having their reactivity compared to the so far most active complex in this class. Cytotoxicity experiments carried out toward human neuroblastoma SH-SY5Y cells confirmed its proapoptosis property. DNA cleavage studies were then performed in the presence of these complexes, in order to verify the influence of ligand structural features in its nuclease activity. All of them were able to cause double-strand DNA scissions, giving rise to nicked circular Form II and linear Form III species, in the presence of hydrogen peroxide. Additionally, DNA Form II was also detected in the absence of peroxide when the most active complex, [Cu(isaepy)(2)](2+) 1, was used. In an effort to better elucidate their interactions with DNA, solutions of the different complexes titrated with DNA had their absorption spectra monitored. An absorbance hyperchromism observed at 260 nm pointed to the intercalation of these complexes into the DNA structure. Further, investigations of 2-deoxy-D-ribose (DR) oxidation catalyzed by each of those complexes, using 2-thiobarbituric acid reactive species (TBARS) method, and detection of reactive oxygen species (ROS) formation by spin-trapping EPR, suggested that their mechanism of action in performing efficiently DNA cleavage occurs preferentially, but not only by oxidative pathways. (C) 2007 Elsevier Inc. All rights reserved.

Incorporation of oxygen into the succinate co-product of iron(II) and 2-oxoglutarate dependent oxygenases from bacteria, plants and humans.

class="Apple-style-span" style="font-family: arial; line-height: 18px;">The ferrous iron and 2-oxoglutarate (2OG) dependent oxygenases catalyse two electron oxidation reactions by coupling the oxidation of substrate to the oxidative decarboxylation of 2OG, giving succinate and carbon dioxide coproducts. The evidence available on the level of incorporation of one atom from dioxygen into succinate is inconclusive. Here, we demonstrate that five members of the 2OG oxygenase family, AlkB from Escherichia coli, anthocyanidin synthase and flavonol synthase from Arabidopsis thaliana, and prolyl hydroxylase domain enzyme 2 and factor inhibiting hypoxia-inducible factor-1 from Homo sapiens all incorporate a single oxygen atom, almost exclusively derived from dioxygen, into the succinate co-product.

On the problem of algebraic completeness for the invariants of the Riemann tensor. II

We study the set of invariants CZ [E. Zakhary and J. Carminati, J. Math. Phys. 42, 1474 (2001)] for the class of space-times whose Ricci tensors do not possess a null eigenvector. We show that all cases are completely backsolvable in terms of sets of invariants from CZ. We provide algebraically complete sets for each canonically different space-time.

Spin-crossover, mesomorphic and thermoelectrical properties of cobalt(II) complexes with alkylated N3-Schiff bases

Three new cobalt(ii) complexes, [Co(L12)2](BF4)2 (1), [Co(L14)2](BF4)2·H2O (2) and [Co(L16)2](BF4)2·H2O (3), where L12-16 are N3-Schiff bases appended with linear C12-16 carbon chains at the nitrogen atoms, were obtained in good yields by facile one-pot reactions. The single crystal X-ray structure of complex 1 shows a tetragonally compressed CoN6 coordination geometry. The melting temperatures of 1-3 were lower than 373 K, while their decomposition temperatures were above 473 K. All complexes have high-spin Co(ii) centres at 300 K and exhibit a columnar mesophase above 383 K. Complexes 1 and 3 showed normal thermal spin-crossover behaviour with weak hysteresis loops at about 320 K. Hence, these complexes showed uncoupled phase transitions (class iiia). The values for the Seebeck coefficient (Se) of the cobalt redox couples formed from 1 and 2 were 1.89 ± 0.02 mV K-1 and 1.92 ± 0.08 mV K-1, respectively, identifying them as potential thermoelectrochemical materials.

Molecular characterization and phylogenetic analysis of JussuMP-I: A RGD-P-III class hemorrhagic metalloprotease from Bothrops jararacussu snake venom

Snake venom metalloproteases (SVMPs) embody zinc-dependent multidomain enzymes responsible for a relevant pathophysiology in envenomation. including local and systemic hemorrhage. The molecular features responsible for hemorrhagic potency of SVMPs have been associated with their multidomains structures which can target these proteins them to several receptors of different tissues and cellular types. BjussuMP-I. a SVMP isolated from the Bothrops jararacussu venom, has been characterized as a P-III hemorrhagic metalloprotease. The complete cDNA sequence of BjussuMP-I with 1641bp encodes open reading frames of 547 amino acid residues, which conserve the common domains of P-III high molecular weight hemorrhagic metalloproteases: (i) pre-pro-peptide, (ii) metalloprotease, (iii) disintegrin-like and (iv) rich cysteine domain. BjussuMP-I induced lyses in fibrin clots and inhibited collagen- and ADP-induced platelet aggregation. We are reporting, for the first time, the primary structure of an RGD-P-III class snake venom metalloprotease. A phylogenetic analysis of the BjussuMP-1 metalloprotease/catalytic domain was performed to get new insights into the molecular evolution of the metalloproteases. A theoretical molecular model of this domain was built through folding recognition (threading) techniques and refined by molecular dynamics simulation. Then, the final BjussuMP-I catalytic domain model was compared to other SVMPs and Reprolysin family proteins in order to identify eventual structural differences, which could help to understand the biochemical activities of these enzymes. The presence of large hydrophobic areas and some conserved surface charge-positive residues were identified as important features of the SVMPs and other metalloproteases. (C) 2006 Elsevier B.V. All rights reserved.

Structural, functional, and bioinformatics studies reveal a new snake venom homologue phospholipase A(2) class

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

População de plantas e espaçamento entre linhas do feijoeiro irrigado. II: rendimento de grãos e componentes do rendimento

O objetivo deste experimento foi avaliar o efeito de diferentes populações de plantas e espaçamentos entre linhas de cultivo na produção de massa seca, rendimento de grãos e componentes do rendimento da cultura do feijoeiro irrigado. O experimento foi conduzido no ano agrícola 1997/1998, em área do Departamento de Engenharia Rural da Universidade Federal de Santa Maria (UFSM), RS. A cultivar de feijão preto BR-FEPAGRO 44 - Guapo brilhante, habito de crescimento indeterminado (tipo II), foi submetida a três populações de plantas (175, 250 e 325 mil plantas há-1) e três espaçamentos entre linhas de cultivo (35, 50 e 65cm). Utilizou-se o delineamento experimental inteiramente casualizado, bifatorial, com quatro repetições. Irrigações por aspersão foram aplicadas quando a evapotranspiração máxima da cultura, estimada a partir da evaporação do tanque classe A, indicava um valor acumulado de 25mm. Os resultados demonstraram que as diferentes populações de plantas e espaçamentos entre linhas de cultivo não ocasionaram alterações no rendimento de grãos e massa de mil sementes. No entanto, o número de sementes por vagem e de vagens por planta aumentaram com a redução na população de plantas. Na fase do enchimento de grãos, a redução do espaçamento entre linhas de cultivo aumentou a massa seca da parte aérea das plantas. A cultivar de feijoeiro, BR-FEPAGRO 44 - Guapo brilhante, apresenta elevada plasticidade dos componentes do rendimento, havendo compensação no rendimento de grãos nas menores populações de plantas com aumento da produção por planta.

Ionic medium effects on equilibrium constants .1. Proton, copper(II), cadmium(II), lead(II) and acetate activity coefficients in aqueous solution

The molar single ion activity coefficients associated with hydrogen, copper(II), cadmium(II) and lead(II) ions were determined at 25 degrees C and ionic strengths between 0.100 and 3.00 M (NaClO4), whereas for acetate the ionic strengths were fixed between 0.300 and 2.00 M, held with the same inert electrolyte. The investigation was carried out potentiometrically by using proton-sensitive glass, copper, cadmium and lead ion-selective electrodes and a second-class Hg\Hg-2(CH3COO)(2) electrode. It was found that the activity coefficients of these ions (y(i)) can be assessed through the following empirical equations:log y(H) = -0.542I(0.5) + 0.451I; log y(Cu) = -1.249I(0.5) + 0.912I; log y(Cd) = -0.829I(0.5) + 0.448I(1.5);log y(Pb) = -0.404I(0.5) + 0.117I(2); and log y(Ac) = 0.0370I .

Gingival margin alterations and the pre-orthodontic treatment amount of keratinized gingiva

The purpose of this retrospective study was to associate the amount of keratinized gingiva present in adolescents prior to orthodontic treatment to the development of gingival recessions after the end of treatment. The sample consisted of the intra-oral photographs and orthodontic study models from 209 Caucasian patients with a mean age of 11.20 ± 1.83 years on their initial records and 14.7 ± 1.8 years on their final records. Patients were either Angle Class I or II and were submitted to non-extraction orthodontic treatment. Gingival recession was evaluated by visual inspection of the lower incisors and canines as seen in the initial and final study models and intra-oral photographs. The amount of recession was quantified using a digital caliper and the observed post-treatment gingival margin alterations were classified as unaltered, coronal migration of the gingival margin or apical migration of the gingival margin. The width of the keratinized gingiva was measured from the mucogingival line to the gingival margin on the pre-treatment photographs. The teeth that developed gingival recession and those that did not have their gingival margin position changed did not differ in relation to the initial amount of keratinized gingiva (3.00 ± 0.61 and 3.5 ± 0.86 mm, respectively). Paradoxically, teeth that presented a coronal migration of the gingival margin had a smaller initial amount of keratinized gingiva (2.26 ± 0.31 mm). The mean amount of initial keratinized gingiva did not predispose lower incisors and canines to gingival recession.

In Vitro and In Vivo Activities of Ruthenium(II) Phosphine/Diimine/Picolinate Complexes (SCAR) against Mycobacterium tuberculosis

Rifampicin, discovered more than 50 years ago, represents the last novel class of antibiotics introduced for the first-line treatment of tuberculosis. Drugs in this class form part of a 6-month regimen that is ineffective against MDR and XDR TB, and incompatible with many antiretroviral drugs. Investments in R&D strategies have increased substantially in the last decades. However, the number of new drugs approved by drug regulatory agencies worldwide does not increase correspondingly. Ruthenium complexes (SCAR) have been tested in our laboratory and showed promising activity against Mycobacterium tuberculosis. These complexes showed up to 150 times higher activity against MTB than its organic molecule without the metal (free ligand), with low cytotoxicity and high selectivity. In this study, promising results inspired us to seek a better understanding of the biological activity of these complexes. The in vitro biological results obtained with the SCAR compounds were extremely promising, comparable to or better than those for first-line drugs and drugs in development. Moreover, SCAR 1 and 4, which presented low acute toxicity, were assessed by Ames test, and results demonstrated absence of mutagenicity. © 2013 Pavan et al.

Structural and functional studies with mytoxin II from Bothrops moojeni reveal remarkable similarities and differences compared to other catalytically inactive phospholipases A2-like

Lys49-phospholipases A2 (Lys49-PLA2s) are proteins found in bothropic snake venoms (Viperidae family) and belong to a class of proteins which presents a phospholipase A2 scaffold but are catalytically inactive. These proteins (also known as PLA2s-like toxins) exert a pronounced local myotoxic effect and are not neutralized by antivenom, being their study relevant in terms of medical and scientific interest. Despite of the several studies reported in the literature for this class of proteins only a partial consensus has been achieved concerning their functional-structural relationships. In this work, we present a comprehensive structural and functional study with the MjTX-II, a dimeric Lys49-PLA2 from Bothrops moojeni venom which includes: (i) high-resolution crystal structure; (ii) dynamic light scattering and bioinformatics studies in order to confirm its biological assembly; (iii) myographic and electrophysiological studies and, (iv) comparative studies with other Lys49-PLA2s. These comparative analyses let us to get important insights into the role of Lys122 amino acid, previously indicated as responsible for Lys49-PLA2s catalytic inactivity and added important elements to establish the correct biological assembly for this class of proteins. Furthermore, we show two unique sequential features of MjTX-II (an amino acid insertion and a mutation) in comparison to all bothropic Lys49-PLA2s that lead to a distinct way of ligand binding at the toxin's hydrophobic channel and also, allowed the presence of an additional ligand molecule in this region. These facts suggest a possible particular mode of binding for long-chain ligands that interacts with MjTX-II hydrophobic channel, a feature that may directly affect the design of structure-based ligands for Lys49-PLA2s. © 2013 Elsevier Ltd.

Antitumour and anti-inflammatory effects of palladium(II) complexes on Ehrlich tumour

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A prática do professor de matemática em classes de recuperação de ciclo II no regime de progressão continuada do estado de São Paulo

Pós-graduação em Educação Matemática - IGCE

O ensino de geometria no ciclo II do ensino fundamental: um estudo analítico

Pós-graduação em Educação - FFC

Ruídos articulares em pacientes parcialmente desdentados (classe I ou II de Kennedy), antes e após a reposição dental com prótese parcial removível: avaliação através da eletrovibratografia

Pós-graduação em Odontologia - FOA