Estratégia de simplificação molecular no planejamento racional de fármacos: a descoberta de novo agente cardioativo

In this article are described examples of the successful use of molecular simplification strategy in the discovery of new drugs from bioactive natural products and synthetic compounds. The discovery of a new cardiotonic derivative (37, 2-thienylidene-3,4-methylenedioxybenzoylhydrazine; LASSBio-294), efficiently synthesized from Brazilian natural product and structurally designed by molecular simplification of active pyridazinone compounds reported in the literature, is described. A brief description of the pharmacological profile of this new cardiotonic lead-compound, belonging to the N-acylhydrazone (NAH) class, is also reported herein.

Química Medicinal: 25 anos de planejamento racional de fármacos

The Sociedade Brasileira de Química is commemorating its 25th anniversary, and this paper is intended to draw an overview of the Brazilian Medicinal Chemistry over all these years. In 1977 Brazil had almost no activities at all in the field, albeit many efforts were already on the way for encouraging Brazilian Scientists to enter the area. Among many different endeavours to help medicinal chemists to fulfil their proposals and the establishment of an on-going research with the help of networks, the Sociedade Brasileira de Química created, in 1991, its own Division on Structure and Activity Relationship, which became the Division of Medicinal Chemistry, in 1997.

Bifosfonatos (BFs) como transportadores osteotrópicos no planejamento de fármacos dirigidos

Drug therapy involving bone tissue diseases is difficult, calling for the design of specific drugs. The present paper is a brief review of a new site-directed system termed ODDS (osteotropic drug delivery system), based on a latenciation process, using bisphosphonates as bone carriers. This is an important tool for the rational prodrug design for obtaining selective drugs.

Identidad territorial y promoción turística: la organización de eventos como estrategia de creación, consolidación y difusión de la imagen de marca del territorio

Gertakizun baten antolaketa paradigmatikoa da in situ bizi izandako lurraldeirudien eraikuntza-prozesuan. Parte-hartzaileen imaginario kolektiboan finkatzeko helburuaz antolatutako gertakizunak direla eta, fabrikatutako lurralde-irudiek – turistikoak zein bestelakoak– sustapen turistikorako alternatiba bitxia planteatzen dute, gertakizunaren kudeaketa-estrategian bertan dagoena. Izan ere, gertakizunak, berez, lurraldearen sustapenerako estrategia garrantzitsua adierazten du; are gehiago, irudien katalizatzaile ere bihur daiteke, eta bere osotasunean hiri-marka bat finkatzeko gai diren imaginarioak sor ditzake. Artikulu honetan, identitate-posizionamenduari eta lurralde-sustapenari dagokienean, gertakizun baten antolaketak eskeintzen dituen aukerak ezagutarazten dira.

Análisis arqueomorfológico de la llanura litoral al Norte de Valencia. Estructuración territorial y revisión de las tramas centuriadas

This paper is the result of the archaeo-morphological analysis of an area located to the north of the city of Valencia (Spain). This research has been developed in the context of one of the author’s PhD, which aims to analyse the whole of the city’s historical territory. The morphology of Valencia’s historical landscape and its different features have been analysed with a diachronic and multidisciplinary approach, combining data obtained from different types of analysis and through methodological procedures based on archaeo-morphology, traditional archaeology and landscape archaeology. For the first time, this methodology has been used in this territory. The results obtained represent a challenge regarding traditionally defended theses.

Anàlisi territorial de la vulnerabilitat dels recursos hídrics davant del canvi climàtic

En aquest capítol es descriuen els mecanismes que determinen la resposta dels sistemes hidrològics al canvi climàtic en el context de Catalunya i propostes per a determinar-ne la vulnerabilitat

Planejamento fatorial aplicado à digestão de amostras de feijão assistida por radiação microondas

The use of factorial design was evaluated for optimization of focused-microwave-assisted digestion of bean samples. Calcium, Fe, Mg, Mn and Zn percentual recoveries were determined in digestates after focused-microwave-assisted digestion according to factorial design procedures. A cavity microwave digestion was carried out to certify the elemental compositions obtained. The accuracy was checked using a standard reference material, the NIST SRM 8433 - Corn Bran. Results are in agreement with certified values at the 95% confidence limit when the Student t-test was used. Volumes of nitric and sulfuric acid, temperature, and the interplay between HNO3 and H2SO4 initial volumes were significant variables according to P-values in the analysis of variance (ANOVA).

Azul de metileno imobilizado na celulose/TiO2 e SiO2/TiO2: propriedades eletroquímicas e planejamento fatorial

The electrochemical properties of methylene blue immobilized on cellulose/TiO2 and mixed oxide SiO2/TiO2 matrices were investigated by means of cyclic voltammetry. The electron mediator property of the methylene blue was optimized using a factorial design, consisting of four factors in two levels. The experimental observations and data analyses on the system indicate that the lowest peak separation occurs for Sil/TiOAM, 1.0 mol L-1 KCl solution and 20 mV s-1 scan rate, while values of current ratio closest to unity were found for Cel/TiOAM independent of electrolyte concentration, 0.2 or 1.0 mol L-1, and scan rate, 20 mV s-1 or 60 mV s-1.

Importância do metabolismo no planejamento de fármacos

It is widely recognized that pharmacokinetic optimization needs to be addressed early in drug discovery to reduce the high failure rate in bringing drugs to market. Poor absorption, too short duration of action due to high elimination rate, or the presence of active metabolites are examples of properties that can potentially lead to unsuccessful clinical programmes. Here I describe a brief overview of advantages and molecular strategies for improving metabolic and pharmacokinetic properties applied to the discovery of fluconazol, beta-blockers, ritonavir and ezetimibe and to the development of the prodrugs enalapril and bambuterol.

Planejamento estatístico de experimentos como uma ferramenta para otimização das condições de biossorção de Cu(II) em batelada utilizando-se casca de nozes pecã como biossorvente

In order to reduce the total number of experiments for achieving the highest amount of adsorbed Cu2+ (qmax) using pecan nutshells (Carya illinoensis) as biosorbent, a full 2(4) factorial design with two central points was carried out (mass of biosorbent- m, pH, initial metallic ion concentration- C0, time of contact- t). In order to continue the optimization of the system, a central composite surface analysis design with two factors and five central points was carried out. The maximum amount of Cu2+ taken up by the pecan nutshells was 20 mg g-1. These results were confirmed by determining a Cu2+ isotherm using the best conditions attained by the statistical design of experiments.

Planejamento participativo no subprograma QEQ do PADCT

The development of the Brazilian chemistry sector, during the last 30 years, is nowadays being attributed to PADCT (Science and Technology Development Program). Since the seventies, the Government took notice of the importance of research in chemistry for the Brazilian economy, therefore creating PADCT to support chemistry and chemical engineering among other areas of science and technology. Planning and implementation of the second phase of this program represented a real joint strategic planning. Since then, academic research and human resources education have experienced significant improvements. However, in the chemical trade, the deficit continues to grow, in spite of an almost constant ratio between importation costs and export revenues. Continued investments for research in the area remain necessary.

Intervenciones de identidad territorial en el proceso global de construcción de imagen de marca de los destinos turísticos

La competitividad emergente entre destinos turísticos ha puesto de manifiesto la necesidad de enfatizar las estrategias de comunicación –con el fin de crear un valor añadido intangible para el potencial cliente- encaminadas a crear una imagen favorable de los espacios que se pretenden promocionar, mediante el diseño de acciones de comunicación con objetivos que van más allá del mero interés promocional o informativo. En este sentido, tanto los emplazamientos que conciben el turismo como una solución de diversificación económica (destinos emergentes), como las localizaciones geográficas que ya disponen de una cierta solera en relación a su tradición turística (destinos maduros), aúnan esfuerzos en aras de consolidar una identidad territorial acorde con sus posibilidades turísticas. Si además se tiene en cuenta que, en la actualidad, el consumo de imágenes percibidas a priori representa, de antemano, un primer viaje simbólico previo a un posterior viaje real, se puede llegar a vislumbrar el papel decisivo que desempeña la interpretación del consumidor (creación de imaginarios individuales y colectivos) en un escenario global de comercialización del territorio. Por tanto, el valor añadido en una situación de dura competencia entre destinos, radica en los valores que se asocian a la imagen de marca turística, que representa la primera carga de sensaciones y emociones que percibe el potencial turista y/o visitante antes de decidirse por uno u otro destino.

Emprego de planejamento fatorial no desenvolvimento de uma metodologia para extração de zinco de resíduos galvânicos

The plating process generates solid waste rich in heavy metals and aiming to reduce environmental impact of such waste, this work suggests a methodology for zinc reduction, through a 2(4) factorial planning, studying the influence of the following variables: acid concentration (15, 20 or 30% v/v), acid type (sulfuric or hydrochloric), acid volume (15, 20 or 25 mL) and extraction time (12, 24 or 36 h). Through this methodology it is possible to establish the optimal conditions (15 mL of a 30% hydrochloric acid concentration during 12 h) to get a 100% efficiency in zinc extraction.

Otimização de metodologia para derivação de desoxinivalenol através de planejamento experimental

The objective of this work was to optimize the derivatization reaction for determining deoxynivalenol (DON) by gas chromatography employing an experimental planning procedure. The factors were: temperature, reaction time, catalyst and trifluoroacetic anhydride concentration. The relative peak areas were used to evaluated the effects. The best conditions for DON derivatization were 200 µL TFAA and 18 mg sodium bicarbonate for 6 min at 74 ºC for 7 to 21 µg of DON. Under these conditions, the detection limit was 1.4 µg of DON.