The role of Polypharmacology and Cholinesterase inhibitors

Publisher Copyright: © 2023 NOVA School of Science and Technology. ChemistrySelect published by Wiley-VCH GmbH.Alzheimer's disease (AD) is a devastating syndrome that accounts for 60–70 % of all dementia cases, putting an enormous burden on global healthcare and economy. Unfortunately, there is no cure for AD, and the currently approved drugs are limited in their effects. Given the various pathological mechanisms behind AD, the “one-target, one-drug” paradigm for drug design became obsolete, and a new paradigm, polypharmacology, emerged. Consequently, a greater focus has been put towards multi-target directed ligands (MTDLs), as these can regulate several targets operating in the disease network. Parallel to that, cholinesterase inhibitors have regained popularity after decades of being considered only symptomatic agents with no disease-modifying properties. In this review, the current AD hypotheses and therapeutic targets, the concept of polypharmacology in AD pathology and the importance of cholinesterases in the pathogenesis and biochemical processes of AD are discussed, with a final overview of the current development in cholinesterase-based MTDLs.publishersversionpublishe

Recent Advances in Sustainable Organocatalysis

The recent advances on green and sustainable organocatalysis are revised in this chapter. An important focus on one of the 12 principles of green chemistry, organocatalysis pursues to reduce energy consumption as well as to optimize the use of different resources, targeting to become a sustainable strategy in organic chemical transformations. In last decades, several experimental methodologies have been performed to make organocatalysis an even greener and sustainable alternative to stoichiometric approaches as well as non-catalytic conditions by the use of benign and friendlier reaction media. In this line, several approaches using water as preferential solvent, alternative solvents such as ionic liquids including chiral ones, deep eutectic solvents, polyethylene glycol (PEG), supercritical fluids and organic carbonates or solvent-free methodologies have been reported. In this chapter, we mainly focus on the recent remarkable advancements in organocatalysis using green and sustainable protocols

Invasive plants: Turning enemies into value

UID/QUI/50006/2020In this review, a brief description of the invasive phenomena associated with plants and its consequences to the ecosystem is presented. Five worldwide invasive plants that are a threat to Portugal were selected as an example, and a brief description of each is presented. A full description of their secondary metabolites and biological activity is given, and a resume of the biological activity of extracts is also included. The chemical and pharmaceutical potential of invasive species sensu lato is thus acknowledged. With this paper, we hope to demonstrate that invasive species have potential positive attributes even though at the same time they might need to be controlled or eradicated. Positive attributes include chemical and pharmaceutical properties and developing these could help mitigate the costs of management and eradication.publishersversionpublishe

Effect of Iodide-Based Organic Salts and Ionic Liquid Additives in Dye-Sensitized Solar Cell Performance

Funding Information: This work was performed under the project PTDC/QUI-QOR/7450/2020 “Organic Redox Mediators For Energy Conversion” through Fundação para a Ciência e a Tecnologia I. P.-FCT. Additional support includes the Associate Laboratory for Green Chemistry–LAQV, financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020). FCT/MCTES is also acknowledged for the National NMR Facility (RECI/BBB-BQB/0230/2012 and RECI/BBB-BEP/0124/2012,) and Ph.D. grants 2020.09047.BD (J.S.), PD/BD/135087/2017 (A.L.P.) and PD/BD/145324/2019/ (G.M.). Publisher Copyright: © 2022 by the authors.The use of ionic liquid and organic salts as additives for electrolyte systems in dye-sensitized solar cells have been widely described in recent years. The tunability of their physical-chemical properties according to the cation–anion selection contributes toward their high efficiencies. For this purpose, several iodide-based organic salts including imidazolium, picolinium, guanidinium and alkylammonium cations were tested using acetonitrile/valeronitrile electrolytes and their photovoltaic parameters were compared. A best efficiency of 4.48% (4.15% for the reference) was found for 1-ethyl-2,3-dimethylimidazolium iodide ([C2DMIM]I) containing electrolyte, reaffirming the effectiveness of these additives. 4-tertbutylpyridine was included into the formulation to further improve the performance while determining which iodide salts demonstrate the highest synergy with this additive. [C2DMIM]I once again proved to be the superior additive, achieving an efficiency of 6.48% (6% for the reference). Electrochemical impedance spectroscopy was employed to elucidate the effects of the various additives, demonstrating the relevance of the counter electrode resistance on device performance. Finally, several computational descriptors for the cationic structures were calculated and correlated with the photovoltaic and resistance parameters, showing that properties related to polarity, namely relative positive charge, molecular polarizability and partition coefficient are in good agreement with the counter-electrode resistance.publishersversionpublishe

Synthetic approaches to a challenging and unusual structure—an amino-pyrrolidine guanine core

Associate Laboratory for Green Chemistry-LAQV, which is financed by national funds from FCT/MCTES (UIDB/50006/2020). Grant number SFRH/BD/136692/2018 from FCT/MCTES.The synthesis of an unreported 2-aminopyrrolidine-1-carboxamidine unit is here described for the first time. This unusual and promising structure was attained through the oxidative decarboxylation of amino acids using the pair of reagents, silver(I)/peroxydisulfate (Ag(I)/S2O82−) followed by intermolecular (in the case of L-proline derivative) and intramolecular trapping (in the case of acyl L-arginine) by N-nucleophiles. The L-proline approach has a broader scope for the synthesis of 2-aminopyrrolidine-1-carboxamidine derivatives, whereas the intramolecular cyclization afforded by the L-acylarginines, when applied, results in higher yields. The former allowed the first synthesis of cernumidine, a natural alkaloid isolated in 2011 from Solanum cernuum Vell, as its racemic form.publishersversionpublishe

Tailings microbial community profile and prediction of its functionality in basins of tungsten mine

In a circular economy concept, where more than 300 million tons of mining and quarrying wastes are produced annually, those are valuable resources, supplying metals that are extracted today by other processes, if innovative methods and processes for efficient extraction of these elements are applied. This work aims to assess microbiological and chemical spatial distribution within two tailing basins from a tungsten mine, using a MiSeq approach targeting the 16S rRNA gene, to relate microbial composition and function with chemical variability, thus, providing information to enhance the efficiency of the exploitation of these secondary sources. The tailings sediments core microbiome comprised members of family Anaerolineacea and genera Acinetobacter, Bacillus, Cellulomonas, Pseudomonas, Streptococcus and Rothia, despite marked differences in tailings physicochemical properties. The higher contents of Al and K shaped the community of Basin 1, while As-S-Fe contents were correlated with the microbiome composition of Basin 2. The predicted metabolic functions of the microbiome were rich in genes related to metabolism pathways and environmental information processing pathways. An in-depth understanding of the tailings microbiome and its metabolic capabilities can provide a direction for the management of tailings disposal sites and maximize their potential as secondary resources

The Extremophile Endolithella mcmurdoensis gen. et sp. nov. (Trebouxiophyceae, Chlorellaceae), a new Chlorella-like Endolithic alga from Antarctica

The McMurdo Dry Valleys constitute the largest ice-free region of Antarctica and one of the most extreme deserts on Earth. Despite the low temperatures, dry and poor soils and katabatic winds, some microbes are able to take advantage of endolithic microenvironments, inhabiting the pore spaces of soil and constituting photosynthesis-based communities. We isolated a green microalga, Endolithella mcmurdoensis gen. et sp. nov, from an endolithic sandstone sample collected in the McMurdo Dry Valleys (Victoria Land, East Antarctica) during the K020 expedition, in January 2013. The single non-axenic isolate (E. mcmurdoensis LEGE Z-009) exhibits cup-shaped chloroplasts, electron-dense bodies, and polyphosphate granules but our analysis did not reveal any diagnostic morphological characters. On the basis of phylogenetic analysis of the 18S rRNA (SSU) gene, the isolate was found to represent a new genus within the family Chlorellaceae.We are sincerely grateful to Antarctica New Zealand for providing logistics support during K020 event. This campaign was conducted as part of the New Zealand Terrestrial Antarctic Biocomplexity Survey (nzTABS) through awards (UOWX0710 and UOWX1401) from the New Zealand Foundation for Research and Technology (FRST), Antarctica New Zealand, and the New Zealand Ministry of Business, Innovation and Employment to SCC. The work was also supported by the Portuguese Science and Technology Foundation (FCT) through grants UID/Multi/04423/2019 to CIIMAR, IF/01358/2014 and PTDC/MAR-BIO/2818/2012 to PNL, PTDC/CTA-AMB/30997/2017 to CM, and PhD scholarships to AR (SFRH/BD/140567/2018).info:eu-repo/semantics/publishedVersio

The mixture of "ecstasy" and its metabolites impairs mitochondrial fusion/fission equilibrium and trafficking in hippocampal neurons, at in vivo relevant concentrations

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a potentially neurotoxic recreational drug of abuse. Though the mechanisms involved are still not completely understood, formation of reactive metabolites and mitochondrial dysfunction contribute to MDMA-related neurotoxicity. Neuronal mitochondrial trafficking, and their targeting to synapses, is essential for proper neuronal function and survival, rendering neurons particularly vulnerable to mitochondrial dysfunction. Indeed, MDMAassociated disruption of Ca2+ homeostasis and ATP depletion have been described in neurons, thus suggesting possible MDMA interference on mitochondrial dynamics. In this study, we performed real-time functional experiments of mitochondrial trafficking to explore the role of in situ mitochondrial dysfunction in MDMA's neurotoxic actions. We show that the mixture of MDMA and six of its major in vivo metabolites, each compound at 10μM, impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria in cultured hippocampal neurons. Furthermore, the overexpression of mitofusin 2 (Mfn2) or dynamin-related protein 1 (Drp1) K38A constructs almost completely rescued the trafficking deficits caused by this mixture. Finally, in hippocampal neurons overexpressing a Mfn2 mutant, Mfn2 R94Q, with impaired fusion and transport properties, it was confirmed that a dysregulation of mitochondrial fission/fusion events greatly contributed to the reported trafficking phenotype. In conclusion, our study demonstrated, for the first time, that the mixture of MDMA and its metabolites, at concentrations relevant to the in vivo scenario, impaired mitochondrial trafficking and increasedmitochondrial fragmentation in hippocampal neurons, thus providing a new insight in the context of "ecstasy"-induced neuronal injury. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.Ministerio de Ciencia e Innovacion (MICINN), Spain (BFU2008-3980); Plan Nacional de Drogas, Spain; Fundação para a Ciência e a Tecnologia (Portugal) (FCT)

First application of core-shell Ag@Ni magnetic nanocatalyst for transfer hydrogenation reactions of aromatic nitro and carbonyl compounds

A magnetically separable core-shell Ag@Ni nanocatalyst was prepared by a simple one-pot synthetic route using oleylamine both as solvent and reducing agent and triphenylphosphine as surfactant. The synthesized nanoparticles were characterized by several techniques such as X-ray diffraction pattern (XRD), high resolution transmission electron microscopy (HR-TEM), selected area electron diffraction (SAED) pattern, and energy dispersive X-ray spectroscopy (EDS). The core-shell Ag@Ni nanocatalyst was found to have very excellent activity for the transfer hydrogenation reactions of aromatic nitro and carbonyl compounds under mild conditions using isopropyl alcohol as hydrogen donor. Excellent chemoselectivity and regioselectivity for the nitro group reduction was demonstrated