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La presente invención se refiere al diseño y síntesis de nuevos fluoróforos con aplicación en el desarrollo de biosensores de fluorescencia, y particularmente, a derivados de 8- metoxi-2-oxo-1,2-dihidrociclopenta[de]quinolina y su aplicación como reactivos de marcaje de la luminiscencia de lantánidos. [ES], The present invention relates to the design and synthesis of new fluorophores that can be used to develop fluorescence biosensors, and particularly, to 8-methoxy-2-oxo-1,2-dihydrocyclopenta[de]quinoline derivatives and the use thereof as reagents for labelling lanthanide luminescence. [EN], Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Granada, A1 Solicitud de patente con informe sobre el estado de la técnica

This work was supported by grant CTQ2017–85658-R funded by MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” and grants PID2019–104366RB-C22 and PID2020–114256RBI00 funded by MCIN/AEI/10.13039/ 501100011033. A.R.-A. thanks the Spanish Ministerio de Educación y Formación Profesional for an FPU Ph.D. studentship., In a recent work, we reported a methodology for imaging the different stages of amyloid aggregation in quantitative multiparametric dual-color fluorescence lifetime imaging (FLIM) and superresolution microscopy by using a pair of dyes capable of binding aggregates and undergoing subsequent intra-aggregate energy transfer (FRET) (RuizArias et al. Sensors Actuat. B, 2022, 350:130882). In this microarticle we present the optimization process for choosing the best pair of dyes through a screening of different naphthalimides and quinolimides and other known amyloid-binding dyes., Spanish Ministerio de Educación y Formación, Grant CTQ2017–85658-R funded by MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa”, Grants PID2019–104366RB-C22 and PID2020–114256RBI00 funded by MCIN/AEI/10.13039/ 501100011033

The lack of polarity sensing fluorophores with OFF-ON features when increasing the environment polarity has limited the monitoring of biological processes that involve an increase in local hydrophilicity. In this work, replacement of a hydroxyl group by a dimethylamino group transformed solvatochromic ICT naphthalimide- and quinolimide-based fluorophores into reversed solvatochromic ones, with higher emission in polar than in apolar environments. Excited-state dynamics studies, TD-DFT calculations, X-ray and NMR support the existence of a folded conformation for the 2-(dimethylamino)ethyl chain upon the imide ring in apolar solvents, where the dimethylamino group would quench the fluorescence by a PET effect, while in polar solvents the chain has an extended conformation, where the PET is hindered. These PET fluorophores have given rise to H2O and pH sensors in organic solvents as well as to bright macrophage cytoplasm imaging probes., The work was supported by the Spanish Ministerio de Economía y Competividad grants SAF2012-32209, FU2015-67284-R, CTQ2017-85658-R, CTQ2015-63997-C2, the CSIC grant 201580E073, and Comunidad Autónoma de Madrid (S2013/MIT2841, Fotocarbon)

[EN] The present invention relates to new derivatives of 5-(2-(1H-indol-3-yl)ethyl-2- piperazin-2-one or pharmaceutically acceptable salts thereof and to combinations of said compounds with other active ingredients, for use in the treatment and/or prevention of viral infections by viruses from the family Coronaviridae, to the use of said compound or its combinations in the manufacture of a medicament for the treatment or prevention of said diseases and to a method of treating and/or preventing said diseases by administration of said compound or its combinations., [FR] La présente invention concerne de nouveaux dérivés de 5-(2-(1H-indol-3-yl)éthyl-2-pipérazin-2-one ou des sels pharmaceutiquement acceptables de ceux-ci et des combinaisons de ces composés avec d'autres principes actifs, destinés à être utilisés dans le traitement et/ou la prévention d'infections virales par des virus de la famille des Coronaviridae, l'utilisation dudit composé ou de ses combinaisons dans la fabrication d'un médicament pour le traitement ou la prévention desdites maladies et un procédé de traitement et/ou de prévention desdites maladies par administration dudit composé ou de ses combinaisons., Consejo Superior de Investigaciones Científicas, A1 Solicitud de patente con informe sobre el estado de la técnica

[ES] La presente invención se refiere a haloacetamidas derivadas de quinolin-2(1H)-onas de fórmula (I), que sensibilizan la luminiscencia de lantánidos, y su aplicación como reactivos de marcaje de la luminiscencia de lantánidos en diversas biomoléculas, entre otras, en péptidos y proteínas., [EN] The present invention relates to haloacetamides derived from quinolin-2 (1H) -ones of formula (I), which sensitize lanthanide luminescence, and their application as labeling reagents for lanthanide luminescence in various biomolecules, among others, in peptides and proteins., Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Granada, B2 Patente con examen previo

Resumen del trabajo presentado al 6th European Chemical Biology Symposium ECBS/LS-EuChemS, celebrado en Madrid (España) del 3 al 5 de abril de 2019., DREAM (Downstream Regulatory Element Antagonist Modulator), also known as KChIP-3 or calsenilin, is a multifunctional calcium binding protein that controls the expression level and/or the activity of several proteins related to calcium homeostasis, neuronal excitability and neuronal survival. As an auxiliary protein in the plasma membrane, DREAM interacts with, and regulates, the gating of KV4 potassium channels, L- and T-type voltage-dependent calcium channels, NMDA receptors and the transcriptor factor ATF6, which is involved in the unfolding protein response machinary. Considering that altered neuronal calcium homeostasis and the accumulation of poorly folded proteins are common features of many neurodegenerative pathologies, the DREAM modulation could open new avenues for the treatment of neurodegenerative diseases. We recently showed that reduced DREAM expression or blockade of DREAM activity by repaglinide is neuroprotective in Huntington's disease (HD)[1]. However, up to now, only three DREAM binding molecules have been identified. Hence, there is a clear need for the development of chemical tools to modulate and characterize DREAM activity and its interactions. In this communication we will report the identification of novel DREAM modulators by following a multidisciplinary strategy that involves structure-based design, organic chemistry, site-directed mutagenesis and in vitro and in vivo experiments. Our findings open a new avenue in the search of effective treatments of neurodegenerative diseases., Spanish Ministery of Economy, Industry and Competitivity (AEI-FEDER, EU grants): BFU2015-67284-R, SAF2017-89554-R, SAF2016-75021-R, SAF2015-66275-C2-2-R; Instituto de Salud Carlos III CIBERNED and CIBERCV programs; the Madrid regional government/Neurodegmodels; and CSIC PIE 201580E073.

The 1,8-naphthalimide scaffold is found among the most fruitful structures in the design of fluorophores with application in the development of fluorescence biosensors, due to its favorable photophysical properties, such as strong absorption and emission, large Stokes shifts, and photostability[1]. Considering that introduction of a nitrogen atom into the 1,8-naphtalimide skeleton could red-shift the fluorescence emission and increase water solubility, we have recently studied the design, synthesis and photophysical properties of 8-methoxy-4,5-quinolimides[2]. The photophysical properties of both scaffolds depend on the attached substituents and can be tuned by chemical manipulation. We have synthesized and will communicate new naphthalimide (A) and quinolimide (B) derivatives with a dimethylaminoethyl chain at the imide nitrogen atom, which behave as macrophage fluorescence sensors. Depending on the nature of the R substituent, these fluorophores can be used to imagine either the macrophage cytoplasm or the nucleus. The nucleus sensors bind DNA as intercalants., The work was supported by the Spanish Ministerio de Economía y Competividad grants SAF2012-32209, FU2015-67284-R, CTQ2017-85658-R, and the CSIC grant 201580E07