Synthesis and biological activities of polyphenolic hybrids - evaluation of anti-cancer, anti-inflammatory and antioxidant activities

Os compostos polifenólicos constituem uma classe de metabolitos secundários de plantas, mas existe também uma enorme quantidade de derivados sintéticos ou semi-sintéticos contendo múltiplas unidades fenólicas. Estes compostos apresentam importantes características biológicas, que dependem das suas estruturas básicas. Certos derivados desta família de compostos, tais como flavonoides, cromonas e cumarinas contribuem para os benefícios da dieta humana, e partilham o núcleo de benzopiran-(2 e 4)-ona ou benzofuran-3-ona. A presente dissertação inclui uma introdução geral e três capítulos que descrevem as novas rotas sintéticas estabelecidas para a preparação de novos híbridos de diversos compostos polifenólicos, assim como a sua elucidação estrutural e termina com a presentação dos resultados da avaliação biológica desses mesmos compostos. No segundo capítulo discute-se a preparação de híbridos de pirimidina- e imidazolidina-polifenóis, especialmente a síntese diastereoseletiva de novos híbridos benzofuran-3-ona-hidantoína e derivados de uracilo. A rota sintética envolve a ação de carbodiimidas sobre os ácidos cromona-(2- e 3)-carboxílicos num só passo ou em dois passos sequenciais, catalisada por uma base orgânica ou inorgânica. O terceiro capítulo descreve reações do tipo adições conjugadas 1,4 - hetero-ciclisações em cascata de compostos 1,3-dicarbonílicos em ácido cromona-3-carboxílico catalisadas por uma base orgânica, que originaram novas cromonas, cromanonas e flavonas polissubstituídas. As bispiranonas [bispiran-2 e 4)-onas] foram elaboradas numa reacção de acoplamento da 4-hidroxicumarina ou da lactona do ácido triacético com o ácido cromona-3-carboxílico ou precursores formil-funcionalizados (ω-formil-2’-hydroxy acetofenonas e cromona-3-carbaldeídos) utilizando organocatálise básica. Finalmente, alargou-se o estudo das adições conjugadas 1,4 para uma variedade de 4-hidroxipiran-2-onas e cetonas α,β-insaturadas para originar novos análogos de warfarina. Obteve-se uma variedade de estruturas complexas por hibridação das unidades de 4-hidroxicumarina ou da lactona do ácido triacético com os novos derivados de cromonas polissubstituídas. Todos as reações foram executadas em condições suaves e ambientalmente favoráveis, utilizando a 4-pirrolidinopiridina como organocatalisador básico. As estruturas dos novos híbridos polifenólicos foram caracterizados por técnicas espectroscópicas de alta resolução, incluindo espectroscopia de ressonância magnética nuclear (1D e 2D) e por difractometria de raios-X, que nos permitiram resolver o complexidade estrutural dos compostos sintetizados. O quarto capítulo apresenta os resultados da avaliação biológica obtidos com os híbridos polifenólicos sintetizados neste trabalho, mostrando a possibilidade de seu envolvimento na terapia do cancro. A maioria dos compostos foram avaliados quanto ao seu efeito sobre a citotoxicidade e proliferação de células leucémicas e ao seu envolvimento na regulação de via pró-inflamatória NF-kB, na qual, os híbridos de biscumarinas exibiram actividades elevadas (IC50 = 6-19 μM para inibição de NF-kB depois de 8 horas de incubação e IC50 = 15-39 μM para efeitos citotóxicos em células cancerosas, após 24 horas de incubação). Uma inibição moderada das enzimas HDAC e Cdc25 foi induzida pelos derivados de benzofuran-3-ona-hidantoína. Catorze dos novos derivados polifenólicos polissubstituídos, tendo como estrutura básica a benzopiran-4-ona, foram avaliados pela sua actividade quimiopreventiva do cancro mediada pela indução de sinalização citoprotectora Nrf2 (fator 2 relacionado com o fator nuclear da proteína E2) e capacidade para inibir a proliferação das células de cancro da mama. Os derivados da classe das cromanonas foram identificados como os indutores mais potentes da actividade Nrf2. As concentrações necessárias para aumentar a actividade de luciferase em 10 vezes (C10) foram de 2,8-21,3 μM. Todos os novos híbridos polifenólicos que apresentam atividade citotóxica e anti-proliferativa não afectam o crescimento de células saudáveis periféricas do sangue (PBMC) (IC50 > 50 μM), indicando a sua seletividade para as células cancerosas e sugerindo que alguns deles são estruturalmente interessantes para posteriores análises. A avaliação da atividade antioxidante utilizando os testes do radical livre DPPH e o poder redutor do ião férrico FRAP foram realizados em algumas estruturas híbridas polifenólicas.

Caracterização da ictiofauna de intertidal rochoso na costa sul de Portugal

Dissertação mest., Biologia Marinha, Universidade do Algarve, 2009

Family agriculture for bottom-up rural development: a case study of the indigenous Mayan population in the Mexican Peninsula

Since pre-colonial times the indigenous communities of Mayan origin in the state of Quintana Roo, Mexico, widely practice home gardens on a sustainable basis as the principal form of family agriculture. This study analyzes the structural complexity, functional diversity and management strategy of these indigenous home gardens in order to attempt to propose recommendations for improved family farming. The Mayan home gardens are structured into three or more vertical layers of multiple plant species of herbs, shrubs and trees, and horizontally into well-defined zones for production of both domestic and wild animals. The home gardens provide multiple services apart from food and nutrition security. For sustainable bottom-up rural development, we recommend the continuation of multifunctional home gardens.

Orientación profesional y situación socio-económica en Argentina. 'Career guidance and socio-economic situation in Argentina'.

Resumen tomado de la publicación. Con el apoyo económico del departamento MIDE de la UNED

Modelling nitrogen fluxes from the land surface to the coastal zone in European systems: the perspective of the INCA project

This paper describes the results and conclusions of the INCA (Integrated Nitrogen Model for European CAtchments) project and sets the findings in the context of the ELOISE (European Land-Ocean Interaction Studies) programme. The INCA project was concerned with the development of a generic model of the major factors and processes controlling nitrogen dynamics in European river systems, thereby providing a tool (a) to aid the scientific understanding of nitrogen transport and retention in catchments and (b) for river-basin management and policy-making. The findings of the study highlight the heterogeneity of the factors and processes controlling nitrogen dynamics in freshwater systems. Nonetheless, the INCA model was able to simulate the in-stream nitrogen concentrations and fluxes observed at annual and seasonal timescales in Arctic, Continental and Maritime-Temperate regimes. This result suggests that the data requirements and structural complexity of the INCA model are appropriate to simulate nitrogen fluxes across a wide range of European freshwater environments. This is a major requirement for the production of coupled fiver-estuary-coastal shelf models for the management of our aquatic environment. With regard to river-basin management, to achieve an efficient reduction in nutrient fluxes from the land to the estuarine and coastal zone, the model simulations suggest that management options must be adaptable to the prevailing environmental and socio-economic factors in individual catchments: 'Blanket approaches' to environmental policy appear too simple. (c) 2004 Elsevier B.V. All rights reserved.

Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of the human breast

Many compounds in the environment have been shown capable of binding to cellular oestrogen receptors and then mimicking the actions of physiological oestrogens. The widespread origin and diversity in chemical structure of these environmental oestrogens is extensive but to date such compounds have been organic and in particular phenolic or carbon ring structures of varying structural complexity. Recent reports of the ability of certain metal ions to also bind to oestrogen receptors and to give rise to oestrogen agonist responses in vitro and in vivo has resulted in the realisation that environmental oestrogens can also be inorganic and such xenoestrogens have been termed metalloestrogens. This report highlights studies which show metalloestrogens to include aluminium, antimony, arsenite, barium, cadmium, chromium (Cr(II)), cobalt, copper, lead, mercury, nickel, selenite, tin and vanadate. The potential for these metal ions to add to the burden of aberrant oestrogen signalling within the human breast is discussed. Copyright (c) 2006 John Wiley & Sons, Ltd.

Non-random reef use by fishes at two dominant zones in a tropical, algal-dominated coastal reef

Habitat use and the processes which determine fish distribution were evaluated at the reef flat and reef crest zones of a tropical, algal-dominated reef. Our comparisons indicated significant differences in the majority of the evaluated environmental characteristics between zones. Also, significant differences in the abundances of twelve, from thirteen analyzed species, were observed within and between-sites. According to null models, non-random patterns of species co-occurrences were significant, suggesting that fish guilds in both zones were non-randomly structured. Unexpectedly, structural complexity negatively affected overall species richness, but had a major positive influence on highly site-attached species such as a damselfish. Depth and substrate composition, particularly macroalgae cover, were positive determinants for the fish assemblage structure in the studied reef, prevailing over factors such as structural complexity and live coral cover. Our results are conflicting with other studies carried out in coral-dominated reefs of the Caribbean and Pacific, therefore supporting the idea that the factors which may potentially influence reef fish composition are highly site-dependent and variable.

Physical properties of palm fruits processed with tools by wild bearded capuchins (Cebus libidinosus)

Habitually, capuchin monkeys access encased hard foods by using their canines and premolars and/or by pounding the food on hard surfaces. Instead, the wild bearded capuchins (Cebus libidinosus) of Boa Vista (Brazil) routinely crack palm fruits with tools. We measured size, weight, structure, and peak-force-at-failure of the four palm fruit species most frequently processed with tools by wild capuchin monkeys living in Boa Vista. Moreover, for each nut species we identify whether peak-force-at-failure was consistently associated with greater weight/volume, endocarp, thickness, and structural complexity. The goals of this study were (a) to investigate whether these palm fruits are difficult, or impossible, to access other than with tools and (b) to collect data on the physical properties of palm fruits that are comparable to those available for the nuts cracked open with tools by wild chimpanzees. Results showed that the four nut species differ in terms of peak-force-at-failure and that peak-force-at-failure is positively associated with greater weight (and consequently volume) and apparently with structural complexity (i.e. more kernels and thus more partitions); finally for three out of four nut species shell thickness is also positively associated with greater volume. The finding that the nuts exploited by capuchins with tools have very high resistance values support the idea that tool use is indeed mandatory to crack them open. Finally, the peak-force-at-failure of the piassava nuts is similar to that reported for the very tough panda nuts cracked open by wild chimpanzees; this highlights the ecological importance of tool use for exploiting high resistance foods in this capuchin species.

Paleomagnetic data and K-Ar ages from Mesozoic units of the Santa Marta massif: A preliminary interpretation for block rotation and translations

We report 6 K-Ar ages and paleomagnetic data from 28 sites collected in Jurassic, Lower Cretaceous and Paleocene rocks of the Santa Marta massif, to test previous hypothesis of rotations and translations of this massif, whose rock assemblage differs from other basement-cored ranges adjacent to the Guyana margin. Three magnetic components were identified in this study. A first component has a direction parallel to the present magnetic field and was uncovered in all units (D 352, I = 25.6, k = 57.35, a95 = 5.3, N = 12). A second component was isolated in Cretaceous limestone and Jurassic volcaniclastic rocks (D = 8.8, I = 8.3, k = 24.71, a95 = 13.7, N = 6), and it was interpreted as of Early Cretaceous age. In Jurassic sites with this component, Early Cretaceous K-Ar ages obtained from this and previous studies are interpreted as reset ages. The third component was uncovered in eight sites of Jurassic volcaniclastic rocks, and its direction indicates negative shallow to moderate inclinations and northeastward declinations. K-Ar ages in these sites are of Early (196.5 +/- 4.9 Ma) to early Late Jurassic age (156.6 +/- 8.9 Ma). Due to local structural complexity and too few Cretaceous outcrops to perform a reliable unconformity test, we only used two sites with (1) K-Ar ages, (2) less structural complexity, and (3) reliable structural data for Jurassic and Cretaceous rocks. The mean direction of the Jurassic component is (D = 20.4, I = -18.2, k = 46.9, a95 = 5.1, n = 18 specimens from two sites). These paleomagnetic data support previous models of northward along-margin translations of Grenvillian-cored massifs. Additionally, clockwise vertical-axis rotation of this massif, with respect to the stable craton, is also documented; the sense of rotation is similar to that proposed for the Perija Range and other ranges of the southern Caribbean margin. More data is needed to confirm the magnitudes of rotations and translations. (C) 2009 Elsevier Ltd. All rights reserved.

Caracterização ecológica dos peixes recifais do Atol das Rocas

The present work was carried out at the Atol das Rocas (3º 51 S; 33º 49 W), the only atoll of the South Atlantic and the first Brazilian marine protected area. It was guided by the following hypothesis: the composition of the fish communities varies in agreement with the position of the pools; in other words, with or without permanent ocean connection. To test the validity of this hypothesis, the fish abundance was estimated in the connected pools (Barretinha/Barreta Falsa) and unconnected ones (Cemiteriozinho/Âncoras), carrying an ecological characterization of the fishes that inhabit these pools. Additionally, the structural complexity of the sampled places was also evaluated intending to verify the variations of the abundance and diversity of fishes in function to this factor. By the fact of this research was being carried out through the limits of a conservation unit, the samples was realized using visual census techniques. The results generated through uni and multivariate analytic techniques allowed the evidence that decisive factor in the density, richness and diversity variations of fishes are linked to the substratum type (Hard / Soft bottom) and not by the fact that the pool are or are not connected permanently to the ocean. In relation to the structural complexity; 58% of the variations in the diversity of fishes were attributed to changes in the structural complexity, while 12% of the variations in the abundance were attributed to the structural complexity

Macrofauna de ambientes não consolidados adjacentes à recifes da área de proteção ambiental dos recifes de corais Rio Grande do Norte, Brasil

This study aimed to characterize, for the first time, the benthic invertebrates that inhabit the region of soft bottoms adjacent to the APARC reefs in order to situate them as an important component of infralittoral coastal areas of Northeast Brazil. Soft bottoms areas of APARC corresponds to infralittoral zones vegetated by seagrass Halodule wrightii and unvegetated infralittoral zones, both subjected to substantial hydrodynamic stress. Through scuba diving, biological and sedimentary samples of both habitats were analyzed, with a cylindrical sampler. We identified 6160 individuals belonging to 16 groups and 224 species. The most abundant macrofaunal group was Polychaeta (43%), followed by Mollusca (25%) and Crustacea (14%), what was expected for these environments. In the first chapter, regarding vegetated areas, we tested three hypotheses: the existence of differences in the faunal structure associated with H. wrightii banks submitted to different hydrodynamic conditions; the occurrence of minor temporal variations on the associated macrofauna of banks protected from hydrodynamic stress; and if the diversity of macrofauna is affected by both benthophagous predators and H. wrightii biomass. It was observed that macrofauna associated at the Exposed bank showed differences in structure when comparing the Protected bank, the granulometry of the sediments, that co-varies with the hydrodynamism, was the cause of these variations. The results also pointed to a lower temporal variation in the macrofaunal structure on the Protected bank and a negative relation between macrofaunal and benthophagous fish abundance. At the Exposed bank, a greater faunal diversity was observed, probably due to the higher seagrass biomass. The second chapter compares the vegetated and non-vegetated areas in order to test the hypothesis that due to greater seasonal stability in tropical environments, seagrass structure would act to distinguish the vegetated and non-vegetated areas macrofauna, over time. It was also expected that depositivores were the most representative invertebrates on non-vegetated environments, on the assumption that the seagrass bank would work as a source of debris to adjacent areas, enriching them. Considering all sampling periods, the total macrofauna abundance and diversity were higher in vegetated areas, when compared to non-vegetated ones. Seasonally, the structural complexity provided by Halodule differentiated more clearly the fauna from vegetated and non-vegetated areas, but only at the climatic extremes, i.e. Dry season (extreme climatic stability, with low hydronamism variation) and Rainy season (great hydrodynamism variation and probably vegetated bank burial). Furthermore, the high organic matter levels measured in the sandy banks coincided with an outstanding trophic importance of deposit feeders, proving the debris-carrying hypothesis. The last chapter focused on the non-vegetated areas, where we tested that the hypothesis infaunal halo in tropical reefs depending on local granulometry. In this context, we also tested the hypothesis that benthophagous fish predation would have an effect on the low abundance of macrofaunal groups due to the high hydrographic stress, thus allowing other predatory groups to have greater importance in these environments. Proving the hypothesis, no spatial variation, both on abundance families neither on community structure, occur along distance of the edge reefs. However, we found that complex combinations of physical factors (grain size and organic matter levels originated from local hydronamic conditions) covary with the distance from the reefs and has stronger influence on macrofauna than considered biological factors, such as predation by benthophagous fishes. Based on the main results, this study shows that unconsolidated areas around APARC reefs are noteworthy from an ecological and conservational point of view, as evidenced by the biota-environment and organismal relations, never before described for these areas

Análises estratigráfica e estrutural da Seção Rifte (Valanginiano ao Barremiano) na área do levantamento sísmico 3D de baixo vermelho, Bacia Potiguar emersa

Baixo Vermelho area, situated on the northern portion of Umbuzeiro Graben (onshore Potiguar Basin), represents a typical example of a rift basin, characterized, in subsurface, by the sedimentary rift sequence, correlated to Pendência Formation (Valanginian-Barremian), and by the Carnaubais fault system. In this context, two main goals, the stratigraphic and the structural analysis, had guided the research. For this purpose, it was used the 3D seismic volume and eight wells located in the study area and adjacencies. The stratigraphic analysis of the Valanginian-Barremian interval was carried through in two distinct phases, 1D and 2D, in which the basic concepts of the sequence stratigraphy had been adapted. In these phases, the individual analysis of each well and the correlation between them, allowed to recognize the main lithofacies, to interpret the effective depositional systems and to identify the genetic units and key-surfaces of chronostratigraphic character. The analyzed lithofacies are represented predominantly by conglomerates, sandstones, siltites and shales, with carbonate rocks and marls occurring subordinately. According to these lithofacies associations, it is possible to interpret the following depositional systems: alluvial fan, fluvio-deltaic and lacustrine depositional systems. The alluvial fan system is mainly composed by conglomerates deposits, which had developed, preferentially in the south portion of the area, being directly associated to Carnaubais fault system. The fluvial-deltaic system, in turn, was mainly developed in the northwest portion of the area, at the flexural edge, being characterized by coarse sandstones with shales and siltites intercalated. On the other hand, the lacustrine system, the most dominant one in the study area, is formed mainly by shales that could occur intercalated with thin layers of fine to very fine sandstones, interpreted as turbidite deposits. The recognized sequence stratigraphy units in the wells are represented by parasequence sets, systems tracts and depositional sequences. The parasequence sets, which are progradational or retrogradational, had been grouped and related to the systems tracts. The predominance of the progradation parasequence sets (general trend with coarsening-upward) characterizes the Regressive Systems Tract, while the occurrence, more frequently, of the retrogradation parasequence sets (general trend with finning-upward) represents the Transgressive System Tract. In the seismic stratigraphic analysis, the lithofacies described in the wells had been related to chaotic, progradational and parallel/subparallel seismic facies, which are associated, frequently, to the alluvial fans, fluvial-deltaic and lacustrine depositional systems, respectively. In this analysis, it was possible to recognize fifteen seismic horizons that correspond to sequence boundaries and to maximum flooding surfaces, which separates Transgressive to Regressive systems tracts. The recognition of transgressive-regressive cycles allowed to identify nine, possibly, 3a order deposicional sequences, related to the tectonic-sedimentary cycles. The structural analysis, in turn, was done at Baixo Vermelho seismic volume, which shows, clearly, the structural complexity printed in the area, mainly related to Carnaubais fault system, acting as an important fault system of the rift edge. This fault system is characterized by a main arrangement of normal faults with trend NE-SO, where Carnaubais Fault represents the maximum expression of these lineations. Carnaubais Fault corresponds to a fault with typically listric geometry, with general trend N70°E, dipping to northwest. It is observed, throughout all the seismic volume, with variations in its surface, which had conditioned, in its evolutive stages, the formation of innumerable structural features that normally are identified in Pendencia Formation. In this unit, part of these features is related to the formation of longitudinal foldings (rollover structures and distentional folding associated), originated by the displacement of the main fault plan, propitiating variations in geometry and thickness of the adjacent layers, which had been deposited at the same time. Other structural features are related to the secondary faultings, which could be synthetic or antithetic to Carnaubais Fault. In a general way, these faults have limited lateral continuity, with listric planar format and, apparently, they play the role of the accomodation of the distentional deformation printed in the area. Thus, the interaction between the stratigraphic and structural analysis, based on an excellent quality of the used data, allowed to get one better agreement on the tectonicsedimentary evolution of the Valanginian-Barremian interval (Pendência Formation) in the studied area

Controlling factors of benthic macroinvertebrates distribution in a small tropical pond, lateral to the Paranapanema River (São Paulo, Brazil).

The aim of the present study was to examine the benthic fauna in a marginal pond lateral to the Paranapanema River and to identify the main controlling factors of its distribution. Considering the small size of the lacustrine ecosystem, we expected that seasonal variations of the benthic community attributes are more important than spatial variations; Methods: Two samplings, one in March and another in August, were carried out at nine sites in the pond. Sediment samples were obtained through a Van Veen grab for invertebrate sorting, granulometric analysis, and for quantification of organic matter in sediment. Other abiotic factors were measured, such as water transparency, dissolved oxygen, pH, electric conductivity, temperature, and depth of sediment sampling sites. Regarding the comparative analysis at spatial scale, no significant variations in density of the benthic invertebrate community were found. Results: In relation to the studied abiotic factors, only depth presented significant differences among sampling sites; All the measured environmental parameters presented significant differences among sampling months, except depth and the physical and chemical characteristics of the sediment. The abundance of Chaoboridae and Chironomidae was the unique attribute with a significant difference in comparing the two months. A higher abundance of taxa occurred in August, especially for Oligochaeta, Nematoda, Chaoboridae, and Chironomidae; Conclusions: Because of the low structural complexity of the studied pond, we concluded that the changes in benthic macroinvertebrate community attributes were mainly due to seasonal effects.

The role of nitric oxide in regulation of the cardiovascular system in reptiles

The roles that nitric oxide (NO) plays in the cardiovascular system of reptiles are reviewed, with particular emphasis on its effects on central vascular blood flows in the systemic and pulmonary circulations. New data is presented that describes the effects on hemodynamic variables in varanid lizards of exogenously administered NO via the nitric oxide donor sodium nitroprusside (SNP) and, preliminary data on the effects of SNP inhibition of nitric oxide synthase (NOS) by L-nitroarginine methyl ester (L-NAME). Furthermore. on hemodynamic variables in the tegu lizard are presented. The findings are compared with previously published data from Our laboratory on three other species of reptiles: pythons (Skovgaard, N., Galli, G., Taylor, E.W., Conlon, J.M., Wang.. T., 2005. Hemodynamic effects of python neuropeptide gamma in the anesthetized python, Python regius. Regul. Pept. 18, 15-26), rattlesnakes (Galli, G., Skovgaard, N., Abe, A.S., Taylor, E.W., Wang, T., 2005. The role of nitric oxide in the regulation of the systemic and the pulmonary vasculature of the rattlesnake, Crotalus durissus terrificus. J. Comp. Physiol. 175B, 201-208) and turtles (Crossley, D.A., Wang, T., Altimiras, J., 2000. Role of nitric oxide in the systemic and pulmonary circulation of anesthetized turtles (Trachemys scripta). J. Exp. Zool. 286, 683-689). These five species of reptiles possess different combinations of division of the heart and structural complexity of the lungs. Comparison of their responses to NO donors and NOS inhibitors may reveal whether the potential contribution of NO to vascular tone correlates with pulmonary complexity and/or with blood pressure. All existing studies oil reptiles have clearly established a potential role for NO in regulating vascular tone in the systemic circulation and NO may be important for maintaining basal systemic vascular tone in varanid lizards, pythons and turtles, through a continuous release of NO. In contrast., the pulmonary circulation is less responsive to NO donors or NOS inhibitors, and it was only in pythons and varanid lizards that the lungs responded to SNP. Both species have a functionally separated heart, so it is possible that NO may exert a larger role in species with low pulmonary blood pressures, irrespective of lung complexity. (C) 2005 Elsevier B.V. All rights reserved.

Fish as Indicators of Disturbance in Streams Used for Snorkeling Activities in a Tourist Region

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)