Convergent Approaches for the Synthesis of the Anti-tumoral Peptide, Kahalalide F. Study of Orthogonal Protecting Groups

Kahalalide compounds are peptides that are isolated from a Hawaiian herbivorous marine species of mollusc, Elysia rufescens, and its diet, the green alga Bryopsis sp. Kahalalide F and its synthetic analogues are the most promising compounds of the Kahalalide family because they show anti-tumoral activity. Linear solid-phase syntheses of Kahalalide F have been reported. Here we describe several new improved synthetic routes based on convergent approaches with distinct orthogonal protection schemes for the preparation of Kahaladide analogues. These strategies allow a better control and characterization of the intermediates because more reactions are performed in solution. Five derivatives of Kahalalide F were synthesized using several convergent approaches.

Preparation of penta-azole containing cyclopeptides: challenges in macrocyclization

Herein is described the synthesis of several analogs of the natural product IB-01211 from concatenated azoles, via a biomimetic pathway based on cyclization-oxidation of serine containing peptides combined with the Hantzsch synthesis. The macrocyclization of rigid peptide compounds 1 and 2 to give IB-01211 and its epimer 12b was explored, and the results are compared here to those previously obtained for the macrocyclization of more flexible structures in the syntheses of YM-216391, telomestatin, and IB-01211. Lastly, the preliminary results of anti-tumor activity screening of the synthesized analogs are discussed.

Total synthesis and antiproliferative activity screening of (±)-aplicyanins A, B and E and related analogs

The first total synthesis of the indole alkaloids ()-aplicyanins A, B and E, plus seventeen analogs, all in racemic form is reported. Modifications to the parent compound included changing the number of bromine substituents on the indole, the groups on the indole nitrogen (H, Me or OMe), and/or the oxidation level of the heterocyclic core tetrahydropyrimidine. Each compound was screened against three human tumor cell lines, and fourteen of the newly synthesized compounds showed considerable cytotoxicity. The assay results were used to establish structure-activity relationships. These results suggest that the acetyl group moiety on the imine nitrogen, and the bromine at position 5 of the indole, are both critical to activity.

Lamellarin D bioconjugates II: synthesis and cellular internalization of dendrimer and nuclear location signal derivatives

The design and synthesis of Lamellarin D conjugates with a nuclear localization signal peptide and a poly(ethylene glycol)-based dendrimer are described. Conjugates 1-4 were obtained in 8-84% overall yields from the corresponding protected Lamellarin D. Conjugates 1 and 4 are 1.4 to 3.3-fold more cytotoxic than the parent compound against three human tumor cell lines(MDA-MB-231 breast, A-549 lung, and HT-29 colon). Besides, conjugates 3, 4 showed a decrease in activity potency in BJ skin fibroblasts, a normal cell culture. Cellular internalization was analyzed and nuclear distribution pattern was observed for 4, which contains a nuclear localization signalling sequence.

Lamellarin D bioconjugates I: synthesis and cellular internalization of PEG-derivatives

Herein is reported the design and synthesis of poly(ethylene glycol) derivatives of Lamellarin D with the aim of modulating their physicochemical properties, and improving the biological activity. Mono-, di- and tri-PEG conjugates with improved solubility were obtained in 18-57% overall yields from the corresponding partially protected phenolic derivatives of Lamellarin D. Conjugates 1-9 were tested in a panel of three human tumor cell lines (MDA-MB-231 breast, A-549 lung and HT-29 colon) to evaluate their cytotoxicity. Several compounds exhibited enhanced cellular internalization, and more than 85% of the derivatives showed a lower GI50 than Lam-D. Furthermore, cell cycle arrest at G2 phase, and apoptotic cell-death pathways were determined for Lamellarin D and these derivatives.

Synthesis and antitumor activity of mechercharmycin A analogues

Several analogs of the cytotoxic thiopeptide IB-01211 or Mechercharmycin A (1) have been synthetized. The cytotoxicity of 1 and the synthetized analogs was evaluated against a panel of three human tumor cell lines. Thiopeptide 1 and the most active derivatives, 2 and 3c, were chosen for further studies like effects on cell cycle progression and induction of apoptosis. Interestingly, the inhibition of cell division and activation of a programmed cell death by apoptosis was detected.

Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D

The marine alkaloid, Lamellarin D (Lam-D), has shown potent cytotoxicity in numerous cancer cell lines, and was recently identified as a potent topoisomerase I inhibitor. A library of open lactone analogs of Lam-D was prepared from a methyl 5,6-dihydropyrrolo[2,1-a]isoquinoline-3- carboxylate scaffold (1) by introducing various aryl groups through sequential and regioselective bromination, followed by Pd(0)-catalyzed Suzuki cross-coupling chemistry. The compounds were obtained in a 24-44% overall yield, and tested in a panel of three human tumor cell lines, MDA-MB- 231 (breast), A-549 (lung), and HT-29 (colon), to evaluate their cytotoxic potential. From these data the SAR study concluded that more than 75% of the open-chain Lam-D analogs tested showed cytotoxicity in a low micromolar GI50 range.

Análisis de datos de accidentes de tráfico mediante soluciones big data y business intelligence

Este proyecto de final de carrera corresponde al área de inteligencia artificial y representa un caso de uso que pretende utilizar datos reales referentes a accidentes de tráfico (datos de accidentes, muertos, heridos, etc.) y analizarlas conjuntamente con datos que puedan tener una posible relación con los accidentes como el parque de vehículos, las temperaturas de la zona de los accidentes, etc. con la finalidad de poder obtener las posibles relaciones causa-efecto.

Risk factors for colorectal cancer in subjects with family history of the disease.

The relationship between lifestyle factors, past medical conditions, daily meal frequency, diet and the risk of 'familial' colorectal cancer has been analysed using data from a case-control study conducted in northern Italy. A total of 1584 colorectal cancer patients and 2879 control subjects were admitted to a network of hospitals in the Greater Milan area and the Pordenone province. The subjects included for analysis were the 112 cases and the 108 control subjects who reported a family history of colorectal cancer in first-degree relatives. Colorectal cancer cases and control subjects with family history were similarly distributed according to sex, age, marital status, years of schooling and social class. Familial colorectal cancer was associated with meal frequency, medical history of diabetes (relative risk, RR = 4.6) and cholelithiasis (RR = 5.2). Significant positive trends of increasing risk with more frequent consumption were observed for pasta (RR = 2.5, for the highest vs the lowest intake tertile), pastries (RR = 2.4), red meat (RR = 2.9), canned meat (RR = 1.9), cheese (RR = 3.5) and butter (RR = 1.9). Significant inverse associations and trends in risk were observed for consumption of poultry (RR = 0.4), tomatoes (RR = 0.2), peppers (RR = 0.3) and lettuce (RR = 0.3). Significant inverse trends in risk with increasing consumption for beta-carotene and ascorbic acid were observed (RR = 0.5 and 0.4 respectively, highest vs lowest intake tertile). These results suggest that risk factors for subjects with a family history of colorectal cancer in first-degree relatives are not appreciably different from recognized risk factors of the disease in the general population.

Risk of hypoglycemia in newborns from mothers with gestacional diabetes

There are not enough previous publications which are focused on mothers with well-controlled gestational diabetes mellitus (GDM) as a risk factor that determines the occurrence of neonatal hypoglycemia. In addition, approaches to blood glucose monitoring have been inconsistent and poorly defined. Our objective is to determine if being a newborn from a mother with well-controlled gestational diabetes (regardless insulin treatment) have a higher risk to develop hypoglycemia than a healthy newborn, using a defined and strict protocol. The project will take place in a regional hospital of Girona. We will recruit from 2014 to 2015 a cohort of 623 infants born in this center without any malformation or any perinatal pathology or complication, selected with a consecutive sampling. We will record sex, ethnicity and gestational age information. We will measure blood glucose levels and anthropometric measurements in newborns always taking into account the presence of well-controlled maternal gestational diabetes or not. Patients will be followed up during 24 hours to determine the incidence of hypoglycemia. We will analyze the contribution between exposure factors that we have studied and the incidence of the outcome using a multivariate analysis

Proyecto de construcción y puesta en marcha de nueva explotación de cebo porcino para 4.000 plazas en el término municipal de La Puebla de Castro (Huesca)

Aquest treball intenta explicar, de forma detallada, tots els materials, obres i processos que s’han de dur a terme per a la construcción d’una nova explotació d’engreix porcí. L’explotació que es projecta tindrà capacitat per a 4.000 places, i s’ubicarà al terme municipal de La Puebla de Castro, província d’Osca. Es tracta d’un projecte d’enginyeria on es descriu el disseny i el càlcul de les diferents edificacions i instal·lacions que formaran part de la futura explotació. Alhora, es realitzen diversos estudis com el de l’impacte ambiental o el de protecció contra incendis, per a complir el que estableix el Codi Tècnic de l’Edificació; i poder sol·licitar la llicència d’activitat per posar en funcionament l’explotació.

Nota tècnica 1: projecte SETRAM

Un dels aspectes més crítics per assolir una definició avançada i realista del sistema SETRAM és la identificació de les tecnologies més adequades per a la localització d’usuaris mòbils, des de les ja existents (aplicables tant a la localització individual com agregada) fins a les més el.laborades per a la seva aplicació específica i exclusiva en aquest sistema.

La defensa del comunal y de los usos colectivos, León (1800-1936): ¿una "economia moral"?

Peer-reviewed

La imagen corporal en danza/movimiento terapia

El cáncer de mama es el tumor más frecuente en la población femenina. El impacto tanto físico como psicológico y social del diagnóstico y los tratamientos quirúrgicos y farmacológicos significan un antes y después en la vida de estas mujeres. Este estudio de tipo descriptivo-exploratorio investiga lo que significa para esta población el haber pasado por esta enfermedad en relación con su imagen corporal y qué es lo que puede aportar la Danza Movimiento Terapia (DMT) para aliviar los síntomas psicológicos y sociales que sienten como consecuencia del impacto de la enfermedad. A través de un cuestionario extenso y un taller de DMT con un grupo de mujeres operadas de cáncer de mama exploramos los diferentes aspectos implicados en la imagen corporal. Los resultados de este estudio exploratorio nos muestran la importancia que tiene para esta población el aspecto relacional que engloba la imagen corporal.

Els dos testaments coneguts de Petit Joan Sarnoto. Edició i notes

En aquest article es repassa sumàriament la nòmina de mestres majors de la catedral de Tortosa fins a la segona dècada del segle XVI i s"analitza concretament el mestratge de Joan Petit Sarnoto, un mestre parisenc que arriba a assolir el càrrec de mestre major de la seu vers el 1514 i l"exerceix fins a la seva mort, esdevinguda el 1520 a la ciutat de València, on també treballava. Es publiquen, així mateix, els dos testaments fins ara coneguts d"aquest pedrapiquer: un del 1517, redactat a Tortosa, que el vincula amb l"escultor René Ducloux, cosí seu, i a un piquer sicilià anomenat Jaume de Petrasancta; i un altre, el definitiu, redactat a València l"any 1520.