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] (...)

Monocarboxylate transport inhibition potentiates the cytotoxic effect of 5-fluorouracil in colorectal cancer cells

Cancer cells rely mostly on glycolysis to meet their energetic demands, producing large amounts of lactate that are extruded to the tumour microenvironment by monocarboxylate transporters (MCTs). The role of MCTs in the survival of colorectal cancer (CRC) cells is scarce and poorly understood. In this study, we aimed to better understand this issue and exploit these transporters as novel therapeutic targets alone or in combination with the CRC classical chemotherapeutic drug 5-Fluorouracil. For that purpose, we characterized the effects of MCT activity inhibition in normal and CRC derived cell lines and assessed the effect of MCT inhibition in combination with 5-FU. Here, we demonstrated that MCT inhibition using CHC (a-cyano-4-hydroxycinnamic acid), DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) and quercetin decreased cell viability, disrupted the glycolytic phenotype, inhibited proliferation and enhanced cell death in CRC cells. These results were confirmed by specific inhibition of MCT1/4 by RNA interference. Notably, we showed that 5-FU cytotoxicity was potentiated by lactate transport inhibition in CRC cells, either by activity inhibition or expression silencing. These findings provide novel evidence for the pivotal role of MCTs in CRC maintenance and survival, as well as for the use of these transporters as potential new therapeutic targets in combination with CRC conventional therapy.

Erratum to: Measurement of the inclusive jet cross-section in proton-proton collisions at s√=7 TeV using 4.5 fb−1 of data with the ATLAS detector

It was found that the non-perturbative corrections calculated using Pythia with the Perugia 2011 tune did not include the effect of the underlying event. The affected correction factors were recomputed using the Pythia 6.427 generator. These corrections are applied as baseline to the NLO pQCD calculations and thus the central values of the theoretical predictions have changed by a few percent with the new corrections. This has a minor impact on the agreement between the data and the theoretical predictions. Figures 2 and 6 to 13, and all the tables have been updated with the new values. A few sentences in the discussion in sections 5.2 and 9 were altered or removed.

Z boson production in p plus Pb collisions at root S-NN=5.02 TeV measured with the ATLAS detector

The ATLAS Collaboration measures the inclusive production of Z bosons via their decays into electron and muon pairs in p+Pb collisions at sNN−−−√=5.02TeV at the Large Hadron Collider. The measurements are made using data corresponding to integrated luminosities of 29.4 and 28.1 nb−1 for Z→ee and Z→μμ, respectively. The results from the two channels are consistent and combined to obtain a cross section times the Z→ℓℓ branching ratio, integrated over the rapidity region ∣∣y∗Z|<3.5, of 139.8±4.8(statistical)±6.2(systematic)±3.8 (luminosity) nb. Differential cross sections are presented as functions of the Z boson rapidity and transverse momentum and compared with models based on parton distributions both with and without nuclear corrections. The centrality dependence of Z boson production in p+Pb collisions is measured and analyzed within the framework of a standard Glauber model and the model's extension for fluctuations of the underlying nucleon-nucleon scattering cross section.

Ação do mononitrato-5 de isossorbida sublingual durante cinecoronariografia. Comparação com o uso de nitroglicerina sublingual

OBJETIVO: Avaliar o efeito sublingual do mononitrato-5 de isossorbida (MN5IS) e nitroglicerina (NTG) sobre o diâmetro luminal de artérias coronárias epicárdicas, pressão arterial média e efeitos colaterais. MÉTODOS: Cinqüenta pacientes foram submetidos a cateterismo cardíaco e cinecoronariografia, na condição inicial e 5min após administração sublingual de MN5IS grupo A (GA) ou NTG grupo B (GB). RESULTADOS: O diâmetro coronário de referência aumentou em ambos os grupos, sem significância estatística entre os mesmos. Nos GA e GB foram demonstrados uma diminuição (1,66mmHg) e um aumento (0,79mmHg) na pressão arterial média, respectivamente (p=0,123). Não foram observados efeitos colaterais com o uso destas drogas. CONCLUSÃO: MN5IS sublingual é uma alternativa à administração de NTG durante cinecoronariografia e representa uma alternativa terapêutica para o tratamento de doença cardíaca isquêmica.

Síntese e testes in vitro de novas pirimido[5,4-d] pirimidinas em células resistentes do cancro coloretal

Dissertação de mestrado em Química Medicinal

As metas curriculares de português: como as percecionam os professores do 5.º e do 7.º anos de escolaridade

Dissertação de mestrado em Ciências da Educação (área de especialização em Supervisão Pedagógica na Educação em Línguas)

Cinemática e dinâmica de engrenagens - 5. Engrenagens de parafuso sem-fim

[Excerto] 5.1. INTRODUÇÃO As engrenagens de parafuso sem-fim pertencem ao grupo das engrenagens torsas1, em que uma das rodas tem a forma de um parafuso (Branco et al., 2009). As engrenagens de parafuso sem-fim podem também ser consideradas como um caso particular das engrenagens helicoidais cruzadas, sendo que a capacidade de carga é maior no caso do parafuso sem-fim (Flores e Gomes, 2014c). A figura 5.1 ilustra uma engrenagem de parafuso sem-fim com roda helicoidal. Na verdade, esta é uma das formas mais simples e mais frequentemente utilizada na prática corrente e que inclui um parafuso cilíndrico e uma roda cilíndrica de dentes helicoidais, daí a designação de parafuso sem-fim roda helicoidal (Niemann, 1971; Drago, 1988). Na grande maioria das aplicações de parafusos sem-fim o ângulo formado pelos eixos do parafuso e da roda é igual a 90º. As engrenagens de parafuso sem-fim não são, em geral, reversíveis, isto é, funcionam apenas quando o veio motor aciona o parafuso sem-fim, uma vez que quando o sistema é acionado pela roda, a engrenagem tende a bloquear2 (Henriot, 1979; Shigley e Uicker, 1980). (...)