The synthesis of new 6-hydrazinopurines as potential anticancer agents

[Excerpt] Purines, such as adenine, are one of the most important naturally occurring nitrogen heterocycles and they are frequently used as bioactive agents.[1,2] The increasing number of synthetic purines reveals the great potential of these compounds as enzyme inhibitors. Protein Kinases have an important regulatory role in cell proliferation, differentiation and signalling processes. Abnormal signal transduction is responsible for devastating diseases such as cancer. All of the protein kinases identified have in common the cofactor ATP indicating that the adenine nucleus is a very important scaffold for discovery of new anti-cancer agents.[3,4] Previous work identified a modest anticancer activity in a family of 6-arylaminopurines. In the view of these results, it seemed reasonable to assume that some interesting anticancer agents might result by replacement of the phenyl group by a secondary amino group linked to the N-6 atom of the adenine moiety. (...)

The synthesis of novel 5-aminoimidazoles derivatives with anticancer activity

[Excerpt] The imidazole nucleus is present in a significant number of biomolecules and the inclusion of this moiety in organic scaffolds is considered an important synthetic strategy in drug discovery.[1] 5-Aminoimidazoles are interesting building blocks in medicinal chemistry since they are key components in many bioactive molecules and their derivatives showed a wide pharmacological potential as anticancer drugs.[1] The hydrazones constitute an important class of biological active drug molecules due to their wide range of pharmacological properties that include antitumoral activities.[2] Amidrazone derivatives could be considered very promising in the perspective of new drug discovery, because they are very effective as building blocks to obtain various heterocycles.[2,3] The α-hydrazononitriles are a special case of compounds belonging to the family of hydrazones that is less common in the literature, but has a great interest due to their pharmacological applications.[4] (...)

Implementação de um novo processo produtivo adequado à introdução faseada de múltiplos produtos

Dissertação de mestrado integrado em Engenharia e Gestão Industrial

Levantamento taxonômico de desmídias (Chlorophyta) do lago Novo (Amapá, Brasil): gêneros Staurastrum, Staurodesmus e Xanthidium

Neste estudo são descritas e ilustradas as espécies de três gêneros de desmídias (Staurastrum, Staurodesmus e Xanthidium) do lago Novo, um ambiente localizado na região dos lagos, na planície costeira do Estado do Amapá. Um total de 35 táxons foi registrado, sendo 23 do gênero Staurastrum, sete do gênero Staurodesmus e cinco do gênero Xanthidium. Todos os táxons apresentados neste trabalho constituem primeira citação para o estado do Amapá.

Pelidnota filippiniae Soula, 2009 (Coleoptera: Melolonthidae: Rutelinae): um novo desfolhador de acácia-australiana, Racosperma mangium (Willd.) Pedley (Fabaceae), na Amazônia Oriental, Brasil

Plantios de acácia-australiana, Racosperma mangium (Willd.) Pedley (Fabaceae), são opção para reflorestamentos comerciais na Amazônia. O trabalho objetiva, pela primeira vez, reportar e descrever injúrias causadas por Pelidnota filippiniae Soula, 2009 (Coleoptera: Melolonthidae: Rutelinae) em plantio experimental em Dom Eliseu, Pará. Observações mensais foram feitas de 2006 a 2009. A maior incidência ocorreu no início do período chuvoso, em outubro e novembro, nos primeiros anos do plantio, quando diferentes intensidades de desfolha foram observadas. Embora danos significativos não tenham sido constatados, P. filippiniae tem potencial para causar prejuízos à cultura. Recomendam-se monitoramentos mensais nesse período e a catação manual do inseto para evitar maiores danos.

Brazil's global aspirations and their implications for the relationship with Argentina in the framework of MERCOSUR

Dissertação de mestrado em Relações Internacionais

Rádio e internet: o desafio pode ser começar de novo

[Excerto] Num livro recente, sob o título As notícias – um manual do utilizador, o filósofo britânico, Alain de Botton, diz-nos que vivemos, no presente, num estado de permanente aborrecimento e confusão. “Todos nos damos conta, com frequência, de estar perante uma notícia de enorme importância que não nos desperta qualquer interesse”, diz o autor, para acrescentar que essa postura tem origem numa formatação narrativa, cada vez mais disseminada, que nos mergulha por breves instantes numa história complexa e que de seguida nos faz avançar para outra experiência semelhante.

Peptaibolin analogues by incorporation of α,α-dialkylglycines: synthesis and study of their membrane permeating ability

Analogues of Peptaibolin, a peptaibol with antibiotic activity, incorporating α,α-dialkylglycines (Deg, Dpg, and Ac6c) at selected positions were synthesised by MW-SPPS and fully characterized. A control analogue incorporating L-alanine was also prepared. The native peptide and the analogues were studied by fluorescence spectroscopy for their membrane permeating activity. Small unilamellar vesicles (SUVs) of egg phosphatidylcholine/ cholesterol (70:30) containing an encapsulated fluorescence probe (6-carboxyfluorescein) were used as membrane models. The assays of carboxyfluorescein release from SUVs upon peptide addition showed that Peptaibolin-Dpg and Peptaibolin-Ac6c are the most active peptides. These results indicate that the structure of the α,α-dialkylglycines is crucial for the membrane permeating ability of these Peptaibolin analogues.

Influência de filtros de ruído dinâmico na perceção das cores utilizando um novo teste de visão das cores

Dissertação de mestrado em Optometria Avançada

Synthesis of polyhydroxylated compounds from Derythrose: enzymatic inhibition studies

Dissertação de mestrado em Química Medicinal

Synthesis of five-membered heterocycles by indirect electrochemical approach in "Green" media

Radical cyclization continues to be a central methodology for the preparation of natural products containing heterocyclic rings. Hence, some electrochemical results obtained by cyclic voltammetry and controlled-potential electrolysis in the study of electroreductive intramolecular cyclization of ethyl (2S, 3R)-2-bromo-3-propargyloxy-3-(2’,3’,4’,6’-tetra-O-acetyl-beta-D-glucopyranosyloxy) propanoate (1a), 2-bromo-3-allyloxy-3-(2’,3’,4’,6’-tetra-O-acetyl-beta-D-glucopyranosyloxy)propanoate (1b), 2-bromo-[1-(prop-2-yn-1-yloxy)propyl]benzene (1c) and [1-bromo-2-methoxy-2-(prop-2’-yn-1-yloxy)ethyl]benzene (1d) promoted by (1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane)nickel(I), [Ni(tmc)]+, electrogenerated at glassy carbon cathodes in ethanol and ethanol:water mixtures containing tetraalkylammonium salts, are presented. During controlled-potential electrolyses of solutions containing [Ni(tmc)]2+ and bromoalkoxylated compounds (1) catalytic reduction of the latter proceeds via one-electron cleavage of the carbon–bromine bond to form a radical intermediate that undergoes cyclization to afford the substituted tetrahydrofurans.

Prisão e sociedade: Um novo balanço

Regressa-se aqui à relação entre prisão e sociedade, examinada num texto anterior (Cunha, 2008) em que se fazia um inventário das articulações entre estes dois termos nos estudos prisionais. Tenta-se agora atualizar esse percurso e acrescentar-lhe novas balizas. O propósito mantém-se: identificar os diferentes níveis e as modalidades possíveis em que a relação entre o mundo intramuros e o mundo extramuros tem sido pensada

Imidazo-benzocrown ether functionalised amino acids: synthesis and fluorimetric chemosensing studies with metal cations

Comunicação em painel - P59

Synthesis, antiangiogenesis evaluation and molecular docking studies of 1-Aryl-3-[(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas: Discovery of a new substitution pattern for type II VEGFR-2 Tyr kinase inhibitors

The synthesis and biological evaluation of novel 1-aryl-3-[2-, 3- or 4-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 3, 4 and 5 as VEGFR-2 tyrosine kinase inhibitors, are reported. The 1-aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 4a-4h, with the arylurea in the meta position to the thioether, showed the lowest IC50 values in enzymatic assays (10-206 nM), the most potent compounds 4d-4h (IC50 10-28 nM) bearing hydrophobic groups (Me, F, CF3 and Cl) in the terminal phenyl ring. A convincing rationalization was achieved for the highest potent compounds 4 as type II VEGFR-2 inhibitors, based on the simultaneous presence of: (1) the thioether linker and (2) the arylurea moiety in the meta position. For compounds 4, significant inhibition of Human Umbilical Vein Endothelial Cells (HUVECs) proliferation (BrdU assay), migration (wound-healing assay) and tube formation were observed at low concentrations. These compounds have also shown to increase apoptosis using the TUNEL assay. Immunostaining for total and phosphorylated (active) VEGFR-2 was performed by Western blotting. The phosphorylation of the receptor was significantly inhibited at 1.0 and 2.5 microM for the most promising compounds. Altogether, these findings point to an antiangiogenic effect in HUVECs.

A systematic study of the structural and magnetic properties of Mn-, Co-, and Ni-Doped Colloidal Fe3O4 nanoparticles

A series of colloidal MxFe3-xO4 (M = Mn, Co, Ni; x = 0–1) nanoparticles with diameters ranging from 6.8 to 11.6 nm was synthesized by hydrothermal reaction in aqueous medium at low temperature (200 °C). Energy-dispersive X-ray microa-nalysis and inductively coupled plasma spectrometry confirms that the actual elemental compositions agree well with the nominal ones. The structural properties of obtained nanoparticles were investigated by using powder X-ray diffraction, Raman scattering, Mössbauer spectroscopy, and electron microscopy. The results demonstrate that our synthesis technique leads to the formation of chemically uniform single-phase solid solution nanoparticles with cubic spinel structure, confirming the intrinsic doping. Magnetic studies showed that, in comparison to Fe3O4, the saturation magnetization of MxFe3-xO4 (M = Mn, Ni) decreases with increasing dopant concentration, while Co-doped samples showed similar saturation magnetizations. On other hand, whereas Mn- and Ni-doped nanoparticles exhibits superparamagnetic behavior at room temperature, ferromagnetism emerges for CoxFe3-xO4 nanoparticles, which can be tuned by the level of Co doping.