Procedimiento de preparación de derivados de tipo arilo-heteroarilo y arilo-arilo y compuestos obtenidos

El objeto de la presente invención es un procedimiento de preparación de derivados de tipo arilo — heteroarilo y arilo - arilo a partir de anilinas o sales de diazonio y de compuestos aromáticos, que pueden ser arilos o heteroarilo, en el cual se utilizan materiales que aportan ácido ascórbico o sus derivados como catalizadores. Constituyen igualmente un objeto de la presente invención los compuestos obtenidos mediante el referido procedimiento.Peer reviewedConsejo Superior de Investigaciones CientíficasA1 Solicitud de adición a la patent

The cardiac torsion as a sensitive index of heart pathology: A model study.

The torsional behaviour of the heart (i.e. the mutual rotation of the cardiac base and apex) was proved to be sensitive to alterations of some cardiovascular parameters, i.e. preload, afterload and contractility. Moreover, pathologies which affect the fibers architecture and cardiac geometry were proved to alter the cardiac torsion pattern. For these reasons, cardiac torsion represents a sensitive index of ventricular performance. The aim of this work is to provide further insight into physiological and pathological alterations of the cardiac torsion by means of computational analyses, combining a structural model of the two ventricles with simple lumped parameter models of both the systemic and the pulmonary circulations. Starting from diagnostic images, a 3D anatomy based geometry of the two ventricles was reconstructed. The myocytes orientation in the ventricles was assigned according to literature data and the myocardium was modelled as an anisotropic hyperelastic material. Both the active and the passive phases of the cardiac cycle were modelled, and different clinical conditions were simulated. The results in terms of alterations of the cardiac torsion in the presence of pathologies are in agreement with experimental literature data. The use of a computational approach allowed the investigation of the stresses and strains in the ventricular wall as well as of the global hemodynamic parameters in the presence of the considered pathologies. Furthermore, the model outcomes highlight how for specific pathological conditions, an altered torsional pattern of the ventricles can be present, encouraging the use of the ventricular torsion in the clinical practice.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.jmbbm.2015.10.00

Molecular Simplification in Bioactive Molecules: Formal Synthesis of (+)-Muconin

7 páginas, 1 figura, 7 esquemas, 1 tabla.-- El PDF es la versión post-print.The concept of molecular simplification as a drug design strategy to shorten synthetic routes, while keeping or enhancing the biological activity of the lead drug, has been applied to (+)-muconin, an acetogenin with remarkable cytotoxicity. A novel approach that enables the stereoselective synthesis of such a natural compound or its enantiomer from a common precursor is described. An additional advantage of the method is complete stereochemical control and the decrease in the number of chemical steps required, thus providing an enhancement of the overall yield. Antiproliferative studies against the human solid tumor cell lines showed that the aliphatic chain-THF/THP fragment of (+)-muconin has modest cytotoxic activity. The strategy opens the way to preparing novel bioactive acetogenin analogues by shorter synthetic routes.The authors thank the MYCT (PPQ2002- 04361-C04-02) of Spain and the Canary Islands Government for supporting this research. F.R.P.C. thanks CajaCanarias for a FPI fellowship. R.C. thanks the Spanish MEC for a FPU fellowship. J.M.P. thanks ICIC for a postdoctoral fellowship.Peer reviewe

Upper and lower spinal cord blood supply : the continuity of the anterior spinal artery and the relevance of the lumbar arteries

Objective: Thoracic and thoracoabdominal aortic repair are still complicated by spinal cord ischemia and paraplegia. The aim of the present article is to present the results of an anatomical study conducted by means of both postmortem injection of the vertebral artery and perfusion of the abdominal aorta. Methods: The spinal cord blood supply was investigated in 51 Caucasian cadavers: in 40 cases a methylene blue solution was hand-injected into the vertebral artery, whereas in the remaining 11 cases the abdominal aorta was perfused with a methylene blue solution by means of a roller pump. The level and side of the arteria radicularis magna and the continuity of the anterior spinal artery were recorded. Results: The anterior spinal artery was a continuous vessel without interruptions along the spinal cord in all 51 cases. The arteria radicularis magna level was variable, ranging from T9 to L5. The arteria radicularis magna arose from a lumbar artery in 36 cases (70.5%) and it was left-sided in 32 cases (62.7%). Conclusions: The anterior spinal artery constitutes an uninterrupted pathway between the vertebral arteries, the arteria radicularis magna, and the posterior intercostal and lumbar arteries. Moreover, the arteria radicularis magna arises from a lumbar artery in most of cases. Therefore, the sacrifice of the intercostal arteries during a thoracic aorta repair could be justified, at least from an anatomical standpoint. However, if an extended thoracoabdominal aortic repair is planned, it may be prudent to preserve the blood flow from the lumbar arteries

Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents

A library of structurally related coumarins was generated through synthesis reactions and chemical modification reactions to obtain derivatives with antiproliferative activity both in vivo and in vitro. Out of a total of 35 structurally related coumarin derivatives, seven of them showed inhibitory activity in in vitro tests against Taq DNA polymerase with IC50 values lower than 250 μM. The derivatives 4-(chloromethyl)-5,7-dihydroxy-2H-chromen-2-one (2d) and 4-((acetylthio)methyl)-2-oxo-2H-chromen-7-yl acetate (3c) showed the most promising anti-polymerase activity with IC50 values of 20.7 ± 2.10 and 48.25 ± 1.20 μM, respectively. Assays with tumor cell lines (HEK 293 and HCT-116) were carried out, and the derivative 4-(chloromethyl)-7,8-dihydroxy-2H-chromen-2-one (2c) was the most promising, with an IC50 value of 8.47 μM and a selectivity index of 1.87. In addition, the derivatives were evaluated against Saccharomyces cerevisiae strains that report about common modes of actions, including DNA damage, that are expected for agents that cause replicative stress. The coumarin derivatives 7-(2-(oxiran-2-yl)ethoxy)-2H-chromen-2-one (5b) and 7-(3-(oxiran-2-yl)propoxy)-2H-chromen-2-one (5c) caused DNA damage in S. cerevisiae. The O-alkenylepoxy group stands out as that with the most important functionality within this family of 35 derivatives, presenting a very good profile as an antiproliferative scaffold. Finally, the in vitro antiretroviral capacity was tested through RT-PCR assays. Derivative 5c showed inhibitory activity below 150 μM with an IC50 value of 134.22 ± 2.37 μM, highlighting the O-butylepoxy group as the functionalization responsible for the activity.This research was supported by CONICET (PIP 11220200101091CO 2021-2023), PICT 2017-0785 Type D of the National Agency for Scientific and Technological Promotion, UNSL (PROICO 02-2620), and RGLP from AvH Foundation. E.F.B.-H. thanks CONICET for doctoral fellowship and specially to Graphic Designer Bruna-Haupt L. for his help. H.A.G. thanks CONICET for belonging to the CIC. We wish thank to Dr. Di Marco N. I. for the genetic material gently provided. C.R.P. thanks CONICET for belonging to the CIC and Alexander von Humboldt Foundation for the different subsidies. We appreciate language revision by staff from the Instituto de Lenguas, UNSL, and specially Mg. Rezzano S.F.M. thanks to the Spanish Ministry of Science (research grant BFU2017-83954-R), ACIISI (research grant ProID2017010167), and FIISC (research grant PIFIIS19/04). C.G. thanks Ministerio de Ciencia, Innovación y Universidades (MCIU) of Spain-European Regional Development Fund (ERDF) (PGC2018-094503-B-C22). This work is a part of the cotutelled (UNSL-ULL) Ph.D. of E.F.B.-H.Peer reviewe

Challenges in assessing and managing multi-hazard risks: A European stakeholders perspective

The latest evidence suggests that multi-hazards and their interrelationships (e.g., triggering, compound, and consecutive hazards) are becoming more frequent across Europe, underlying a need for resilience building by moving from single-hazard-focused to multi-hazard risk assessment and management. Although significant advancements were made in our understanding of these events, mainstream practice is still focused on risks due to single hazards (e.g., flooding, earthquakes, droughts), with a limited understanding of the stakeholder needs on the ground. To overcome this limitation, this paper sets out to understand the challenges for moving towards multi-hazard risk management through the perspective of European stakeholders. Based on five workshops across different European pilots (Danube Region, Veneto Region, Scandinavia, North Sea, and Canary Islands) and an expert workshop, we identify five prime challenges: i) governance, ii) knowledge of multi-hazards and multi-risks, iii) existing approaches to disaster risk management, iv) translation of science to policy and practice, and v) lack of data. These challenges are inherently linked and cannot be tackled in isolation with path dependency posing a significant hurdle in transitioning from single- to multi-hazard risk management. Going forward, we identify promising approaches for overcoming some of the challenges, including emerging approaches for multi-hazard characterisation, a common understanding of terminology, and a comprehensive framework for guiding multi-hazard risk assessment and management. We argue for a need to think beyond natural hazards and include other threats in creating a comprehensive overview of multi-hazard risks, as well as promoting thinking of multi-hazard risk reduction in the context of larger development goals