Identification of GSK3186899/DDD853651 as a Preclinical Development Candidate for the Treatment of Visceral Leishmaniasis

The leishmaniases are diseases that affect millions of people across the world, in particular visceral leishmaniasis (VL) which is fatal unless treated. Current standard of care for VL suffers from multiple issues and there is a limited pipeline of new candidate drugs. As such, there is a clear unmet medical need to identify new treatments. This paper describes the optimization of a phenotypic hit against Leishmania donovani, the major causative organism of VL. The key challenges were to balance solubility and metabolic stability while maintaining potency. Herein, strategies to address these shortcomings and enhance efficacy are discussed, culminating in the discovery of preclinical development candidate GSK3186899/DDD853651 (<b>1</b>) for VL

Smart trees. Reusing UMA´s waste: un árbol biotecnológico para mejorar entornos docentes universitarios y ofrecer servicios conectivos

Resumen en inglés: At present, climate change will affect not only natural ecosystems, but also strongly threatens our urban environment, so mitigation work is necessary in our cities. Aware of this, the Smart Campus Vice-Rectorate of the University of Malaga (UMA) is working to make its Campus more environmentally friendly, sustainable, more technological, healthier and friendlier. Within this idea, the project presented here, framed within SDG 13 (Climate Action) is called “Smart-tree”. This is aimed at creating a relaxed and friendly co-working space, where nature (mainly plants) provides a microclimate of environmental and sensory comfort, and access technology to renewable energy and information is able. At the same time, the space is also intended to generate a friendly green atmosphere of leisure and recreation. It is widely known and proven that the benefits provided by green spaces to citizens are multiple: reduction of noise pollution, increase in evapotranspiration, decrease in wind when making a barrier effect, increase in the biodiversity of the area and increase in perceptual and sensory quality (landscape, environmental, aesthetic and aromatic qualities). The development of the project is being carried out by an interdisciplinary group of professors from the university knowledge areas of Architecture, Communications Engineering, Industrial Engineering Design and Botany, as well as students (through the elaboration of their final degrees works and final projects of Master) in the surroundings of the Teatinos Campus of the UMA (Malaga city, Spain). The structure of the Smart-Tree and its furniture have been designed to be built, based on the “re-using” of campus materials that have exhausted their first useful life (circular economy). For this, a catalogue of obsolete materials has been made, from both the different centres and the warehouses that the UMA has available and where there is material that can be used again. Therefore, it is possible to increase the life cycle of the products and decrease the use of new resources, achieving eco-efficiency in an nZEB (“Nearly Zero Energy Buildings”) prototype. In order to create the space and therefore provide it with plants that generate a new environmental and sensory microclimate, a proposal based on the use of primarily native flora has been developed and also considering the water requirement, maintenance needs, functionality, moments were flowering occurs and the ability to fix carbon. Taking all this into account, and through the use of Geographic Information Systems (GIS), the design of the most optimal nature tuning of the structure and surrounding area has been developed. The Smart-Tree also belongs to the IoT (Internet Of Things) and Smart-Campus paradigms, with the aim of apply the potential of Information and Communication Technologies (ICT) to monitor and guide its management in an efficient and ecological way. In this way, the necessary mechanisms for the monitoring of various environmental and energy variables through a near-range IoT system have been established in the Smart-Tree. This system has been designed based on the modification and appropriate hardware for the measurement of the desired variables and a system that allows the visualization of this information obtained in a web address. A small photovoltaic solar installation has also been defined in line with the nature of the project, which will provide infrastructure users with access to clean and sustainable electricity, in addition to meeting the energy needs of the aforementioned data collection system. As a result, the Smart-Tree space is being built in the environment of the Faculty of Sciences of the UMA, under the environmental and sustainability premises pursued. Specifically, the space has been located in the NW area of the Faculty, next to the Central Research Support Services (SCAI) and is in the assembly phase.En la actualidad, el cambio climático amenaza no sólo a los ecosistemas naturales, también a nuestro entorno urbano, por lo que se hace necesaria una labor de mitigación de éste en las ciudades. Conscientes de ello, desde la UMA se está trabajando por hacer un Campus más sostenible, más saludable y más tecnológico. Dentro de esa idea, surge el proyecto presentado, enmarcado dentro del ODS 13 denominado como “SMART-TREE”. Éste tiene por objetivo la creación de un espacio de “co-working”, que aporte un microclima de confort ambiental y sensorial, y la tecnología de acceso a las energías renovables y a la información. A la vez, también se pretende que el espacio contenga una atmósfera verde (fundamentalmente a base de plantas). El espacio se está ejecutando en el entorno de la Facultad de ciencias de la UMA y está siendo construido a través de materiales reutilizados (economía circular). El espacio está siendo naturado, dotándolo de plantas que generen un nuevo microclima ambiental y sensorial. Se ha elaborado una propuesta basada en la utilización de flora fundamentalmente autóctona y se atendió al requerimiento hídrico, las necesidades de mantenimiento, la funcionalidad, los momentos de floración. También se está dotando de toda la teconología TIC necesaria dentro de los despliegues de IoT (Internet Of Things) y Smart-Campus, con el objetivo de aprovechar las potencialidades TIC para monitorizar y guiar la gestión del mismo de un modo eficiente y ecológico. Este sistema ha sido diseñado partiendo de la determinación y hardware adecuado para la medición de las variables deseadas y un sistema que permite la visualización de esta información obtenida en una dirección web. También se ha dimensionado una pequeña instalación solar fotovoltaica, que proporcionará a los usuarios de la infraestructura el acceso a energía eléctrica limpia y sostenible, además de satisfacer las necesidades energéticas del sistema de toma de datos.Ayuda del Plan Propio de Investigación de la UMA: va a servir para justificar su solicitud, debe incluir en este campo: Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech