Synthesis and biological activity of a new class of antitumor cyclopeptides based on the solomonamides

Solomonamides A (1) and B (2) are novel natural products recently isolated from the marine sponge Theonella swinhoei [1]. Preliminary structural studies revealed an unprecedented cyclic peptide type structure. Interestingly, solomonamide A exhibits anti-inflammatory activity, showing potent reduction (60%) of inflammation at a very low concentration of 100 µg/kg in animal models. However, the scarcity of these compounds from their natural sources has been a drawback for further pharmacological assays. In fact, the anti-inflammatory activity of solomonamide B was not evaluated due to the limited amounts. This difficulty to access large amounts of these compounds makes quite difficult to gain insight into their biological profiles and mechanism of action and justifies the chemical synthesis of this new class of cyclic peptides. As a consequence, the solomonamides have been the subject of several synthetic efforts [2] notably by the Reddy group who has recently reported the first total synthesis of solomonamide B based on a intramolecular Heck reaction, which led to a revision of the initially proposed structure for 2 [3].Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Antitumor and antiangiogenic potential of solomonamide synthesis intermediates

Es comunicación (formato panel) a congreso internacionalIn this work we developed a new synthetic strategy towards the solomonamides. a novel class of cyclopeptides of marine origin. The described synthetic approach utilized an olefin metathesis reaction to form the [15]-membered ring contained in these natural products. During the synthetic process, a diverse set of analogues was generated and we evaluated their potential antitumor activity in vitro. For this purpose we performed in vitro proliferation assays, determining the IC50 values of the compounds in a panel of tumor cell lines. In addition, we evaluated the possible antiangiogenic effects of these solomonamide analogues by using in vitro endothelial cell differentiation assays. Our results showed that the potential antitumor and antiangiogenic activity of the studied analogues depended on their chemical structure, suggesting that the presence of specific functional groups could be responsible of their biological activity. Further studies are needed to understand the basis of the observed activities in endothelial and tumor cells.Our experimental work is supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). This communicaction has the support of a travel grant "Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Exploring the ring-closing metathesis for the construction of the solomonamide macrocyclic core: identification of bioactive precursors

New synthetic strategies directed toward the novel cyclopeptides solomonamides have been explored utilizing an olefin metathesis as the key reaction. In the various strategies investigated, we worked on minimally oxidized systems, and the olefin metathesis reaction demonstrated efficiency and validity for the construction of the macrocyclic core. The described synthetic strategies toward the solomonamides are well suited for the subsequent access to the natural products and represent flexible and diversityoriented routes that allow for the generation of a variety of analogues via oxidative transformations. In addition, preliminary biological evaluations of the generated solomonamide precursors revealed antitumor activity against various tumor cell lines.This work was financially supported by the Ministerio de Economía y Competitividad (MINECO) (ref BIO2014-56092-R, CTQ2014-60223-R and CTQ2016-76311-R) and Junta de Andalucía and “Fondo Europeo de Desarrollo Regional-FEDER” (P12 CTS-1507). I.C.-S. thanks Ministerio de Educación, Cultura y Deporte for a predoctoral fellowship (FPU programme)

Visualization of Iron-Binding Micelles in Acidic Recombinant Biomineralization Protein, MamC

Biological macromolecules are utilized in low-temperature synthetic methods to exert precise control over nanoparticle nucleation and placement. They enable low-temperature formation of a variety of functional nanostructured materials with properties often not achieved via conventional synthetic techniques. Here we report on the in situ visualization of a novel acidic bacterial recombinant protein, MamC, commonly present in the magnetosome membrane of several magnetotactic bacteria, including Magnetococcus marinus, strain MC-1. Our findings provide an insight into the self-assembly of MamC and point to formation of the extended protein surface, which is assumed to play an important role in the formation of biotemplated inorganic nanoparticles. The self-organization of MamC is compared to the behavior of another acidic recombinant iron-binding protein, Mms6.This work was supported by the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Materials Sciences and Engineering Division. The research was performed at the Ames Laboratory, which is operated for the U.S. Department of Energy by Iowa State University under Contract no. DE-AC02-07CH11358. MamC cloning and purification were done at the University of Granada, Spain. Concepción Jiménez López acknowledges the support from the Spanish Government through Grant CGL2010-18274 and the program Salvador de Madariaga

Resistencia antimicrobiana en bacterias del grupo Bacteroides fragilis aisladas a partir de muestras diarreicas de pacientes pediátricos y geriátricos costarricenses

Se determinó el perfil de susceptibilidad de 13 aislamientos del grupo Bacteroides fragilis, recuperados en medios selectivos diferenciales a partir de 6 de 31 muestras diarreicas de niños y 3 de 8 muestras de ancianos hospitalizados, mediante un sistema comercial y la técnica de microdilución en caldo. Tres aislamientos de niños presentaron concentraciones mínimas inhibitorias (CMI) de penicilina mayores a 256 µg ml-1 y varios aislamientos fueron resistentes a mezclas de β- lactámicos con inhibidores de β-lactamasas. La resistencia a cefalosporinas se documentó mediante el hallazgo de dos aislamientos de niños con CMI de de 128 µg de cefotaxime ml-1. Un aislamiento de niños y dos de ancianos exhibieron CMI de clindamicina mayores o iguales a 32 µg ml-1, en tanto que dos cepas de niños y una de ancianos se asociaron con CMI de metronidazol mayores a 128 µg ml-1 o de 16 µg ml-1, respectivamente. Se observaron algunas discrepancias entre los resultados de sensibilidad antimicrobiana obtenidos por ambos métodos. El conocimiento de esta resistencia es relevante porque algunas de estas drogas son muy utilizadas en Costa Rica y porque las especies del grupo B. fragilis pueden fungir como un reservorio de genes de resistencia a nivel intestinal

Experimental setup and procedure for the measurement of the 7Be(n,p)7Li reaction at n_TOF

Following the completion of the second neutron beam line and the related experimental area (EAR2) at the n_TOF spallation neutron source at CERN, several experiments were planned and performed. The high instantaneous neutron flux available in EAR2 allows to investigate neutron induced reactions with charged particles in the exit channel even employing targets made out of small amounts of short-lived radioactive isotopes. After the successful measurement of the 7Be(n,) cross section, the 7Be(n,p)7Li reaction was studied in order to provide still missing cross section data of relevance for Big Bang Nucleosynthesis (BBN), in an attempt to find a solution to the cosmological Lithium abundance problem. This paper describes the experimental setup employed in such a measurement and its characterization.Séptimo Programa Marco de la Comunidad Europea de la Energía Atómica (Euratom)-Proyecto CHANDA (No. 605203)Narodowe Centrum Nauki (NCN)-UMO-2012/04/M/ST2/00700-UMO-2016/22/M/ST2/00183Croatian Science Foundation-HRZZ 168

Risk factors for major adverse cardiovascular events in postmenopausal women: UK Biobank prospective cohort study

Background and aims Cardiovascular risk increases during menopause, so the medical and scientific community should consider women's specific risk factors to prevent cardiovascular disease. This study aims to assess the risk factors for the incidence of major adverse cardiovascular events (MACE) exclusive to postmenopausal women. Methods We conducted a prospective cohort study in postmenopausal women aged 40 years and older, who were included in the UK Biobank cohort between 2006 and 2010 and followed to 2021 (12 years). A total of 156,787 women were followed for a median of 12.5 years (nearly 2 million person-years), and MACE risk was assessed using Fine-Gray competing risk models. Results The cumulative incidence of cardiovascular morbidity and mortality was 1.2% (0.97 cases per 1000 women-years). Not having taken birth control pills, not having children, and early menarche (≤12 years) were independently associated with cardiovascular morbidity and mortality. Conclusions Risk factors for cardiovascular disease that are specific to women include early menarche, not having taken oral contraceptives, and reproductive history, and this relationship is independent of classic cardiovascular risk factors

Naturally lignan-rich foods: a dietary tool for health promotion?

Dietary guidelines universally advise adherence to plant-based diets. Plant-based foods confer considerable health benefits, partly attributable to their abundant micronutrient (e.g., polyphenol) content. Interest in polyphenols is largely focused on the contribution of their antioxidant activity to the prevention of various disorders, including cardiovascular disease and cancer. Polyphenols are classified into groups, such as stilbenes, flavonoids, phenolic acids, lignans and others. Lignans, which possess a steroid-like chemical structure and are defined as phytoestrogens, are of particular interest to researchers. Traditionally, health benefits attributed to lignans have included a lowered risk of heart disease, menopausal symptoms, osteoporosis and breast cancer. However, the intake of naturally lignan-rich foods varies with the type of diet. Consequently, based on the latest humans’ findings and gathered information on lignan-rich foods collected from Phenol Explorer database this review focuses on the potential health benefits attributable to the consumption of different diets containing naturally lignan-rich foods. Current evidence highlight the bioactive properties of lignans as human health-promoting molecules. Thus, dietary intake of lignan-rich foods could be a useful way to bolster the prevention of chronic illness, such as certain types of cancers and cardiovascular disease

Documentos sobre Enrique IV de Castilla y su tiempo. Volumen I

El libro ofrece una colección de 4.152 documentos de la época de Enrique IV de Castilla (1454-1474) editados de forma resumida, entresacados de diversos archivos españoles. La mayor parte procede de las colecciones bibliográficas y documentales de la Real Academia de la Historia, como las de Luis de Salazar y Castro, Salvá, Lorich, Catedrales de España y colección Diplomática Española, sin olvidar algunos manuscritos singulares de la misma biblioteca. Igualmente se han vaciado algunos fondos de la Biblioteca Nacional de Madrid y Archivo General de Simancas, así como del Archivo Municipal de Sevilla. El marco cronológico se ha ampliado a los últimos años del reinado de Juan II y primeros de los Reyes Católicos debido a la abundancia de noticias relacionadas con este rey. El criterio temático es flexible, ya que no se ha limitado la búsqueda a la documentación expedida por la cancillería regia. Esta obra pretende ofrecer una herramienta de trabajo a los especialistas en el siglo XV castellano

Multimode Equivalent Network for Boxed Multilayer Arbitrary Planar Circuits

The multimode equivalent network (MEN) formulation has been originally developed for the efficient and accurate analysis of waveguide devices. In this article, we extend the use of the MEN to the analysis of zero-thickness, planar printed circuits in a metallic enclosure. The formulation is developed for metallic areas of arbitrary shape and includes both internal and external ports in the transverse plane to model connections to external components, and coaxial input/output ports. The boundary integral resonant mode expansion (BI-RME) method is used for the analysis of the arbitrary shape metallizations. On this basis, shielded multilayered microstrip circuits of complex geometry are analyzed in the common frame of the MEN technique. To validate the theoretical formulation, several boxed microstrip structures are analyzed, including multilayered configurations with several metallization interfaces, showing good agreement with respect to both other commercial tools, and measurements.This work was supported in part by the Spanish Government through the Ministerio de Educación, Cultura y Deporte under Grant FPU15/02883 and in part by the Ministerio de Economía y Competitividad through the sub-projects 4, 2, and 1 of the coordinated project under Grant TEC2016-75934-C4-R