Synthesis and Antileishmanial Activity of 1,2,4,5-Tetraoxanes against Leishmania donovani

A chemically diverse range of novel tetraoxanes was synthesized and evaluated in vitro against intramacrophage amastigote forms of Leishmania donovani. All 15 tested tetraoxanes displayed activity, with IC50 values ranging from 2 to 45 µm. The most active tetraoxane, compound LC140, exhibited an IC50 value of 2.52 ± 0.65 µm on L. donovani intramacrophage amastigotes, with a selectivity index of 13.5. This compound reduced the liver parasite burden of L. donovani-infected mice by 37% after an intraperitoneal treatment at 10 mg/kg/day for five consecutive days, whereas miltefosine, an antileishmanial drug in use, reduced it by 66%. These results provide a relevant basis for the development of further tetraoxanes as effective, safe, and cheap drugs against leishmaniasis.This research was funded by Fundação para a Ciência e a Tecnologia (FCT), and FEDER/COMPETE 2020-UE, through projects UID/Multi/04326/2019 (Centre of Marine Sciences-CCMAR) and PTDC/MAR-BIO/4132/2014.info:eu-repo/semantics/publishedVersio

Caracterização do Trabalho Experimental Realizado no Ensino Secundário e Estudo da Importância do mesmo na Aprendizagem da Química

A Química, enquanto disciplina individual ou integrada na disciplina de Ciências Físico- Químicas, atravessa tempos difíceis. Considerada pelos alunos uma disciplina difícil, ela é, muitas vezes, preterida em relação a outras onde conseguem obter melhores resultados. Contudo, a Química dispõe de um recurso com potencialidades enormes no que se refere à motivação dos alunos: o Trabalho experimental. Nos currículos é-lhe atribuído um papel preponderante, contudo, na prática, verifica-se que nem sempre isso acontece. Verificar até que ponto existem condições nas escolas para a sua concretização e para que os professores reconheçam essa importância e a ponham em prática, são questões que devemos colocar e às quais pretendemos, com a realização deste estudo, dar resposta. Caracterizar o tipo de Trabalho Experimental que é realizado nas Escolas Secundárias e avaliar qual a importância que ainda lhe é atribuída, por professores e alunos, constituíram, por isso, os grandes objectivos deste estudo. Este estudo, desenvolvido no âmbito da elaboração da dissertação de Mestrado em Química em Contexto Escolar foi efectuado com professores que leccionaram a disciplina de Física e Química A, e alunos que frequentaram esta disciplina no 10º e 11º ano, no ano lectivo 2008/2009. Foi alargado a Escolas, públicas e privadas, de várias regiões do País, com o intuito de obter um maior leque de resultados e de estudar eventuais diferenças. A metodologia seguida baseou-se recolha de dados através da aplicação de inquéritos por questionário, tendo sido os d analisados com recurso a métodos de Descoberta de Conhecimento em Bases de Dados. Optou-se pela Aproximação de Vizinhanças na tarefa de segmentação e pelas Árvores de Decisão para gerar modelos explicativos dos segmentos encontrados, de forma a atribuir um novo caso a um dado segmento. Os resultados obtidos permitiram concluir que, independentemente da metodologia seguida, dos maiores ou menores recursos, a aposta na actividade do aluno e na realização de actividades experimentais constitui uma estratégia muito rica numa disciplina como a Química que é, por excelência, uma ciência experimental

Semigroup presentations for test local groups

In this paper we exhibit a type of semigroup presentations which determines a class of local groups. We show that the finite elements of this class generate the pseudovariety LG of all finite local groups and use them as test-semigroups to prove that LG and S, the pseudovariety of all finite semigroups, verify the same kappa-identities involving kappa-terms of rank at most 1, where kappa denotes the implicit signature consisting of the multiplication and the (omega-1)-power.Fundação para a Ciência e a Tecnologia (FCT), under the project PEst-C/MAT/UI0013/2011European Regional Development Fund, through the programme COMPET

Semidirect product with an order-computable pseudovariety and tameness

Dedicated to the memory of Walter Douglas Munn.The semidirect product of pseudovarieties of semigroups with an ordercomputable pseudovariety is investigated. The essential tool is the natural representation of the corresponding relatively free profinite semigroups and how it transforms implicit signatures. Several results concerning the behavior of the operation with respect to various kinds of tameness properties are obtained as applications.ESF programme “Automata: from Mathematics to Applications (AutoMathA)”.Project PTDC/MAT/65481/2006, which is partly funded by the European Community Fund FEDER.Fundação para a Ciência e a Tecnologia (FCT) through the Centro de Matemática da Universidade do Porto and Centro de Matemática da Universidade do Minh

Studies on the properties of Celluclast/Eudragit L-100 conjugate

A cellulase from Trichoderma reesei was immobilized on Eudragit L-100, a reversibly soluble polymer depending on the pH of the medium. The solubility of the modified cellulase was studied at different pH values. By changing the pH, the adsorption equilibrium of the derivatized proteins is switched towards the liquid phase, thus making recycling possible. This method allows for improved stability, without major loss of specific activity. The adsorption of cellulase on Eudragit lowers the enthalpy of denaturation, but affects only slightly the denaturation temperature. The use of carbodiimide was ineffective on linking the enzymes covalently to the polymer, since the immobilization process was found to be only mediated by non-covalent forces.INCO-DC (96-2205) - OLONOCO

On the ordeal of quinolone preparation via cyclisation of aryl-enamines; synthesis and structure of ethyl 6-methyl-7-iodo-4-(3-iodo-4-methylphenoxy)-quinoline-3-carboxylate

Recent studies directed to the design of compounds targeting the bc(1) protein complex of Plasmodium falciparum, the parasite responsible for most lethal cases of malaria, identified quinolones (4-oxo-quinolines) with low nanomolar inhibitory activity against both the enzyme and infected erythrocytes. The 4-oxo-quinoline 3-ester chemotype emerged as a possible source of potent bc(1) inhibitors, prompting us to expand the library of available analogs for SAR studies and subsequent lead optimization. We now report the synthesis and structural characterization of unexpected ethyl 6-methyl-7-iodo-4-(3-iodo-4-methylphenoxy)quinoline-3-carboxylate, a 4-aryloxy-quinoline 3-ester formed during attempted preparation of 6-methyl-7-iodo-4-oxo-quinoline-3-carboxylate (4-oxo-quinoline 3-ester). We propose that the 4-aryloxy-quinoline 3-ester derives from 6-methyl-7-iodo-4-hydroxy-quinoline-3-carboxylate (4-hydroxy-quinoline 3-ester), the enol form of 6-methyl-7-iodo-4-oxo-quinoline-3-carboxylate. Formation of the 4-aryloxy-quinoline 3-ester confirms the impact of quinolone/hydroxyquinoline tautomerism, both on the efficiency of synthetic routes to quinolones and on pharmacologic profiles. Tautomers exhibit different cLogP values and interact differently with the enzyme active site. A structural investigation of 6-methyl-7-iodo-4-oxo-quinoline-3-carboxylate and 6-methyl-7-iodo-4-hydroxy-quinoline-3-carboxylate, using matrix isolation coupled to FTIR spectroscopy and theoretical calculations, revealed that the lowest energy conformers of 6-methyl-7-iodo-4-hydroxy-quinoline-3-carboxylate, lower in energy than their most stable 4-oxo-quinoline tautomer by about 27 kJ mol(-1), are solely present in the matrix, while the most stable 4-oxo-quinoline tautomer is solely present in the crystalline phase.Fundacao para a Ciencia e Tecnologia (FCT - Portugal) [UID/Multi/04326/2013]; QREN-COMPETE-UE; CCMAR; FCT [SFRH/BD/81821/2011, RECI/BBB-BQB/0230/2012, UI0313/QUI/2013, UID/FIS/04564/2016]; FEDER/COMPETE-UE; [PTDC/QEQ-QFI/3284/2014 - POCI-01-0145-FEDER-016617]info:eu-repo/semantics/publishedVersio

La ceràmica grisa de la granja cistercenca d'Ancosa

Durant l'excavació arqueològica que s'ha dut a terme a la granja cistercenca d'Ancosa (municipi de la Llacuna, comarca d'Anoia), els estius dels anys 1981, 1982 i 1983, han aparegut prop de mil fragments de ceràmica grisa. Aquesta excavació, inclosa dins dels treballs del Departament d'Història Medieval de la Universitat de Barcelona, fou subvencionada pel Servei d'Arqueologia de la Generalitat de Catalunya. Al petit altiplà d'Ancosa, situat entre el Penedès i la comarca d'Anoia, els monjos cistercencs de Valldaura (Valles Occidental) -provinents del monestir de la Grand Selva, del Llenguadoc- reberen, I'any 1155, del comte Ramon Berenguer IV uns drets. Es construïren algunes edificacions -potser se n'aprofità alguna de més vella- i, almenys, alguns membres de la comunitat sembla que hi visqueren alguns anys. Tanmateix, les característiques del lloc feren que aviat els monjos prenguessin la decisió de traslladar-se a Santes Creus, on s'establiren, definitivament, vers el 116