http://hdl.handle.net/10174/29584 2026-06-04T19:50:17Z http://hdl.handle.net/10174/42079 Title: Exploring the potential of new acetylated unsaturated Oxindole derivatives as multi-target inhibitors for BACE1 and BuChE Authors: Carreiro, Elisabete; Montargil, Catarina; Pinto, Mariana; Resende, A.; Santos, A.; Garcia-Sousa, A.; Burke, Anthony J. Abstract: Alzheimer’s disease (AD) is the most common form of dementia worldwide, accounting for an estimated 60–70 % of cases. β-secretase 1 (BACE1), is one of the main therapeutic targets involved in the disease’s pathology, as it is involved in the production of amyloid β. Butrylcholinesterase (BuChE) which is active in the advanced stages of the disease, is targeted for symptomatic relief. AD is a complex illness that needs to be tackled from different angles for which the Multi-target inhibitor approach is a viable current strategy. This work focuses on the development of novel acyl-oxindole molecules – some containing fluorine units, obtained via a structure-based drug design approach, for inhibition of BACE1 and BuChE. This study explored the development of a sustainable metal-based synthetic procedure for rapid and sustainable assess of libraries of these new oxindole derivatives. The compounds were screened to determine their ability to inhibit BACE1, and demonstrated reasonable levels of inhibition, with some of these inhibitors being selected for docking studies to determine the binding mode to the target’s active site. One of the key molecules 12a underwent a cytotoxicity screen in a mouse neuroblastoma cell line expressing the APPswe protein (N2A-APPswe cells) and was an inhibitor of both AChE and BuChE (more potent against the latter, including the human version). Some compounds (3a, 3b, 3i and 12a) have shown moderate BuChE inhibitory activity. 2025-01-01T00:00:00Z http://hdl.handle.net/10174/42071 Title: Spatial Distribution, Health Risks and Heavy Metal Pollution Assessment of Surface Water Under Multiple Anthropogenic Stressors: Case Study in Middle Moulouya Watershed, Morocco Authors: Carreiro, Elisabete; Rachid, Z.; Nordine, N.; Krime, A.; Soufiane, H.; Hamza, E. F. Abstract: The worldwide issue of surface water contamination by heavy metals is a matter of great concern, as it has the potential to affect human health. This study intended to compute heavy metal contamination and human health risks in surface water using the following pollution indices: heavy metal pollution index (HPI), contamination index (CI), metal index (MI), ecological risk index (ERI), human health risk and statistical analysis. For this purpose, eleven water samples were gathered and analyzed by ICP-AES for trace metals such as Pb, As, Zn, Cd, Cu, and Ni. The results showed that heavy metal concentrations varied significantly throughout the study area, with Pb, As, and Cd levels exceeding the WHO limits for drinking purposes. Pollution indices indicated low to high water contamination, with HPI results ranging from 16.41 to 862.18 and from 12.76 to 774.03, above the critical value of 100, requiring serious interventions to reduce heavy metal pollution. MI results range from 0.90 to 20.92 and from 0.70 to 18.41 and CI values range from 0.34 to 20.38 and from 0.15 to 17.86 in the dry and wet periods, respectively, with different contamination levels observed throughout the study area; ERI showed low to considerable ecological risk. Nonetheless, the non-carcinogenic risk, THI < 1, indicates low health risks, while the carcinogenic risk for As and Cd was significantly higher than the negligible threshold of 10−6 , suggesting tolerable health risks. However, managing the contaminated area and minimizing the metal concentrations and predominant routes through which metals impact human health should be priorities for long-term development and to establish a favorable environment. 2025-01-01T00:00:00Z http://hdl.handle.net/10174/42070 Title: How Deep Eutectic Solvents are currently Shaping Asymmetric Catalysis Authors: Carreiro, Elisabete; Burke, Anthony; Federsel, H.-J. Abstract: Asymmetric catalysis is a key technology that provides enantiomerically pure compounds that are vital for the pharmaceutical, agrochemical and food and fragrance industries. It has been recently observed that asymmetric catalysis can be successfully conducted in sustainable systems known as Deep Eutectic Solvents (DESs) or natural deep eutectic solvents (NADESs) when biobased materials are used. This paper provides a critical perspective on these systems, exploring their limitations and relevance for the production and development of new pharmaceuticals and other high-value-added substances. It also looks are very recent developments in this area, whereby, the actual DES can act as the catalyst, the reactant and be part of a supramolecular construct, known as EutectoGel that enhances the sustainability of the process. 2025-01-01T00:00:00Z http://hdl.handle.net/10174/41398 Title: Exploring cation size effects in eutectic solventes: an experimental and molecular Dynamics approach Authors: Moreira, Mariana H.; Duarte, Aimone J. C.; Branco, Luís C.; Marrucho, Isabel M. Abstract: Eutectic solvents (ES) represent a promising class of environmentally friendly solvents, yet many aspects of their structural characteristics remain poorly understood. In this study, we have used molecular dynamics (MD) simulations in combination with experimental data to investigate the molecular structure and physicochemical properties of eutectic systems formed by combining carboxylic salts of sodium, potassium, and lithium with fatty acids. Our results highlight the key role of the cation in molecular arrangement, with the analysis revealing that metal cations promote interactions between salt and acid molecules. In addition, we observed that the size of the ionic radius significantly influences the eutectic point, to the extent that the eutectic may not be detected depending on the metal selected. 2025-01-01T00:00:00Z