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Digital.CSIC (162.855 recursos)

Repositorio institucional del Consejo Superior de Investigaciones Científicas. Digital.CSIC es un depósito de documentos digitales, cuyo objetivo es organizar, archivar, preservar y difundir en modo de acceso abierto la producción intelectual resultante de la actividad investigadora del CSIC.

(IQM) Artículos post-print

Mostrando recursos 1 - 20 de 34

  1. Neurogenic potential assessment and pharmacological characterization of 6-Methoxy-1,2,3,4-tetrahydro-β-carboline (Pinoline) and Melatonin-Pinoline Hybrids

    Fuente Revenga, Mario de la; Pérez, Concepción; Morales-García, José A.; Alonso-Gil, Sandra; Pérez Castillo, Ana; Yáñez, Matilde; Rodríguez-Franco, María Isabel
    This work received the honour of being the Cover of the ACS Chemical Neuroscience in its issue of May 2015

  2. Chalcones as positive allosteric modulators of α7 nicotinic acetylcholine receptors: A new target for a privileged structure

    Balsera, Beatriz; Mulet Soler, José; Fernández-Carvajal, Asia; Torre-Martínez, Roberto de la; Ferrer-Montiel, Antonio; Hernández-Jiménez, José G.; Estévez-Herrera, Judith; Borges, Ricardo; Freitas, Andiara E.; López, Manuela G.; García-López, M. Teresa; González-Muñiz, Rosario; Pérez de Vega, M. Jesús; Valor, Luis M.; Svobodová, Lucie; Sala, Salvador; Sala, Francisco; Criado, Manuel
    The α7 acetylcholine nicotine receptor is a ligand-gated ion channel that is involved in cognition disorders, schizophrenia, pain and inflammation among other diseases. Therefore, the development of new agents that target this receptor has great significance. Positive allosteric modulators might be advantageous, since they facilitate receptor responses without directly interacting with the agonist binding site. Here we report the search for and further design of new positive allosteric modulators having the relatively simple chalcone structure. From the natural product isoliquiritigenin as starting point, chalcones substituted with hydroxyl groups at defined locations were identified as optimal and specific promoters of α77...

  3. Barriers about double carbon-nitrogen bond in imine derivatives (aldimines, oximes, hydrazones, azines)

    Blanco, F.; Alkorta, Ibon; Elguero, José
    The paper presents the results referring to the inversion mechanism of imines and their derivatives (hydrazones, oximes, azines). The calculated barriers [B3LYP/6-311++G(d,p) and G3B3)] are in good agreement with the scarce existing data. The transition states correspond in all cases to a pure nitrogen inversion except in the case of azines where they have some rotation character. The electron properties of the minima and the transition states have been characterized, allowing explanation of the geometrical changes observed in the process.

  4. Multitarget cannabinoids as novel strategy for Alzheimer disease

    González-Naranjo, Pedro; Campillo, Nuria E.; Pérez, Concepción; Páez, Juan A.
    During the last years the development of approaches to multitarget drug design and discovery is gaining acceptance. The cannabinoids are potentially excellent multi-target drug candidates because of their interesting pharmacological profiles, among which stands out the dual capacity of cannabinoid ligands to act as cannabinoid agonist and cholinesterase inhibitors. In this article, inhibition, kinetics studies and docking simulations with a representative set of cannabinoids are presented. The results of these studies showed the inhibitory capacity of some agonist cannabinoids with selectivity at AChE or BuChE enzymes. The kinetic and modelling studies allowed us to postulate the potential mode of action...

  5. De novo designed library of linear helical peptides: An exploratory tool in the discovery of protein-protein interaction modulators

    Bonache de Marcos, María Ángeles; Balsera, Beatriz; López-Méndez, Blanca; Millet, Óscar; Brancaccio, Diego; Gómez-Monterrey, Isabel; Carotenuto, Alfonso; Pavone, Luigi M.; Reille-Seroussi, Marie; Gagey-Eilstein, Nathalie; Vidal, Michel; Torre-Martínez, Roberto de la; Fernández-Carvajal, Asia; Ferrer-Montiel, Antonio; García-López, M. Teresa; Martín-Martínez, Mercedes; Pérez de Vega, M. Jesús; González-Muñiz, Rosario
    Protein-protein interactions (PPIs) have emerged as important targets for pharmaceutical intervention because of their essential role in numerous physiological and pathological processes, but screening efforts using small-molecules have led to very low hit rates. Linear peptides could represent a quick and effective approach to discover initial PPI hits, particularly if they have inherent ability to adopt specific peptide secondary structures. Here, we address this hypothesis through a linear helical peptide library, composed of four sublibraries, which was designed by theoretical predictions of helicity (Agadir software). The 13-mer peptides of this collection fixes either a combination of three aromatic or two...

  6. Artificial neural networks based on CODES descriptors in pharmacology: Identification of novel trypanocidal drugs against chagas disease

    Guerra, Ángela; González-Naranjo, Pedro; Campillo, Nuria E.; Cerecetto, Hugo; González, Mercedes; Páez, Juan A.
    A supervised artificial neural network model has been developed for the accurate prediction of the anti-T. cruzi activity of heterogeneous series of compounds. A representative set of 72 compounds of wide structural diversity was chosen in this study. The definition of the molecules was achieved from an unsupervised neural network using a new methodology, CODES program. This program codifies each molecule into a set of numerical parameters taking into account exclusively its chemical structure. The final model shows high average accuracy of 84% (training performance) and predictability of 77% (external validation performance) for the 4:4:1 architecture net with different training...

  7. Synthesis and pharmacological evaluation of new (E)- and (Z)-3-aryl-4-styryl-1H-pyrazoles as potential cannabinoid ligands

    Silva, V. L. M.; Silva, A. M. S.; Pinto, Diana C. G. A.; Rodríguez, P.; Gómez, M.; Jagerovic, Nadine; Callado, L. F.; Cavaleiro, José A. S.; Elguero, José; Fernández-Ruiz, Javier
    New (Z)- and (E)-1-alkyl-3-(2-hydroxyphenyl)-4-styryl-1H-pyrazoles and (Z)- and (E)-3(5)-(2-alkyloxyphenyl)-4-styryl-1H-pyrazoles were prepared by alkylation of (Z)- and (E)-3(5)-(2-hydroxyphenyl)-4-styryl-1H-pyrazoles with a long chain alkyl bromide in basic medium. The affinity of these alkylated pyrazoles to both human CB1 and CB2 type cannabinoid receptors was evaluated. The results showed that some of them exhibit affinity towards CB1 cannabinoid receptors in the nanomolar range. © ARKAT USA, Inc.

  8. Protonation effects on the chemical shifts of Schiff bases derived from 3-hydroxypyridin-4-carboxaldehyde

    Sanz, D.; Perona, Almudena; Claramunt, Rosa M.; Pinilla, Elena; Torres, M. R.; Elguero, José
    The behavior of Schiff bases derived from 3-hydroxypyridin-4-carboxaldehyde and two N-aminoheterocycles in acid media is described. 1H, 13C, 15N NMR chemical shifts establish the different protonation sites and their influence on the hydroxyimino/oxoenamino tautomerism.

  9. High resolution NMR of free radicals: 13C magic angle spinning of two solid organic free radicals derived from 4,5-dihydro-1H-imidazol-3-oxide- 1-oxyl and theoretical calculation of their NMR properties

    María, D. S.; Claramunt, Rosa M.; Vasilevsky, S. F.; Klyatskaya, S. V.; Alkorta, Ibon; Elguero, José
    The 13C CPMAS NMR spectra of two 4,4,5,5-tetramethyl-2-(1H- and 2H-pyrazol-3-yl)-2-imidazoline-1-oxyl-3-oxides have been recorded and their signals assigned, through unrestricted density functional theory (UDFT) calculations of their absolute shieldings, with satisfactory results. ©ARKAT USA, Inc.

  10. N-substituted-1,2,3-triazoles: Synthesis, characterization and evaluation as cannabinoid ligands

    Oliva, C. G.; Jagerovic, Nadine; Goya, Pilar; Alkorta, Ibon; Elguero, José; Cuberes, R.; Dordal, Alberto
    A series of new N1-, N2-and N3-substituted 1,2,3-triazole derivatives has been synthesized by cycloaddition of butyltin azide with substituted alkynes followed by a N-alkylation reaction. The regioisomers have been isolated and characterized using NMR techniques. GIAO/B3LYP calculations of the absolute shieldings have been performed to verify the assignments and so the structures have been unequivocally identified. The proportion in which the three isomers are obtained corresponds with the relative order of stability indicated by the energy values calculated at the B3LYP level. CB1 cannabinoid receptor binding assays have been performed but none of the compounds showed significant activity. © ARKAT...

  11. Anti-HIV-1 activity of benzothiadiazine dioxide

    Martínez, Ana; Gil, Carmen; Castro, Ana; Pérez, Concepción; Witvrouw, M.; Pannecouque, C.; Balzarini, Jan; De Clercq, Erik
    Antiviral assays carried out on the potent benzothiadiazine dioxide (BTD) human cytomegalovirus (HCMV) inhibitors have led us to find marginal but selective anti-HIV-1 activity. Specific pharmacological studies, such as time of addition experiments and assays on specific viral strains with mutations on its reverse transcriptase, have indicated that BTD compounds act as nonnucleoside reverse transcriptase inhibitors. Theoretical calculations showed a butterfly conformation for the active derivatives that are compatible with their mechanism of action. Therefore, BTD derivatives can be considered as potential lead compounds for the treatment of opportunistic HCMV infections in immunocompromised individuals such as AIDS patients.

  12. Benzothiadiazine dioxide human cytomegalovirus inhibitors: Synthesis and antiviral evaluation of main heterocycle modified derivatives

    Martínez, Ana; Gil, Carmen; Castro, Ana; Bruno, Ana M.; Pérez, Concepción; Prieto, Columbiana; Otero, Joaquín
    The benzothiadiazine dioxide derivatives are potent non-nucleoside human cytomegalovirus (HCMV) inhibitors. As part of our comprehensive structure-activity relationship (SAR) study of these compounds, we have now proposed structural modifications on the heterocyclic moiety both on the number and the nature of the fused heterocycle and on the kind of heteroatoms present on it. Synthesis of these new compounds (benzyl derivatives of thiadiazines, thienothiadiazines, benzothienothiadiazines and quinazolines) and the antiviral evaluation against HCMV has been performed. SAR investigation on this class of compounds has defined the structural requirements for potency and toxicity. They have revealed two important clues: i) a fused...

  13. Cannabinoids and neuropathic pain.

    Goya, Pilar; Jagerovic, Nadine; Hernández-Folgado, Laura; Martín, M. Isabel
    After a brief overview of the endocannabinoid system (CB receptors, and endocannabinoids) and of the cannabinergic ligands, some general issues related to cannabinoids and pain are commented. Finally, the most important findings regarding cannabinoids and neuropathic pain are discussed in detail.

  14. Synthesis of oxazolo[3,2-b]hetero[1,2,4]thiadiazine S,S-dioxides

    Vega, Salvador; Arranz, María Esther; Arán, Vicente J.
    Six bromomethyl derivatives of the new 2,3-dihydrooxazolo[3,2-b]thieno[3,4- e][1,2,4]thiadiazine 5,5-dioxides, 2,3-dihydrooxazolo[3,2-e]thieno[2,3-e][1,2,4] thiadiazine 5,5-dioxides and 6,7-dihydrooxazolo-[3,2-e]pyrazolo[4,3-e][1,2,4] thiadiazine 9,9-dioxides heterocyclic ring systems were synthesized. These compounds are good intermediates for the preparation and development of promising antiviral and psychotropic drugs. The structures of the products are supported by different nmr spectroscopic methods and mass spectrometry.

  15. Synthesis of new hetero[1,2,4]thiadiazin-3-one S,S-dioxides and Oxazolo[3,2-b]hetero[1,2,4]thiadiazine S,S-dioxides as potential psychotropic drugs

    Vega, Salvador; Arranz, María Esther; Arán, Vicente J.
    A series of 2-substituted 2H-thieno[3,4-e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxides (2), 2-substituted 2H-thieno[2,3-e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxides (3), 2-substituted 4,6-dihydropyrazolo[4,3-e]-[1,2,4]thiadiazin- 3(2H)-one 1,1-dioxides (4), 2-substituted 2,3-dihydrooxazolo[3,2-e]thieno[3,4-e] -[1,2,4]thiadiazine 5,5-dioxides, (5), 6-substituted 6,7-dihydro-2H-oxazolo[3,2- b]pyrazolo[4,3-e][1,2,4]thiadiazine 9,9-dioxides (6) and 7-substituted 6,7-dihydro-2H-oxazolo[3,2-e]pyrazolo[4,3-e][1,2,4]thiadiazine 9,9-dioxides (7) were synthesized as potential psychotropic agents.

  16. The present and future of drug discovery for Chagas disease | Presente y futuro en el descubrimiento de fármacos para la enfermedad de Chagas

    Campillo, Nuria E.; González-Naranjo, Pedro; Páez, Juan A.
    Chagas disease, also known as American trypanosomiasis, is caused by infection with the Trypanosoma cruzi. The Pan American Health Organization (PAHO) estimates that 7.7 million persons currently have T. cruzi infection in the 21 endemic countries. This disease can be transmitted to humans by insect vectors that are found only in the American continent, mainly, in rural areas with unhealthy housing conditions where poverty is a general concern. Nifurtimox and benznidazole are the only drugs used against this disease, but sometimes they are not available. The treatment of Chagas disease with nifurtimox or benznidazole is unsatisfactory because of their limited...

  17. Electrochemical, ESR and theoretical insights into the free radical generation by 1,1'-hydrocarbylenebisindazoles and its evaluation as potential bio-active compounds

    Aguilera-Venegas, Benjamín; Olea-Azar, Claudio A.; Arán, Vicente J.; Maya, Juan D.; Kemmerling, U.; Speisky, H.; Mendizábal, F.
    A comprehensive multidisciplinary study is conducted here in order to assess the electrochemical behavior of a series of 1,1'-hydrocarbylenebisindazoles derivatives and its potential use as anti-T.cruzi drugs. At first, we have determined the electrochemical reduction mechanisms of this family by cyclic voltammetry (CV) studies, from which three kind of reduction mechanisms -depending on the substituent at positions 3 and 3'- were established, but sharing a first common step corresponding to the generation of a nitro anion radical, which was corroborated by ESR spectroscopy, showing a comparable hyperfine splitting pattern and a strong influence on the ESR spectral linewidths due to...

  18. Discovery of new antimalarials from commercial drugs by in silico and in vitro screening | Descubrimiento de nuevos antimaláricos a partir de fármacos conocidos mediante cribado in silico e in vitro

    Tugores, Y. M.; Marcel, A. M.; Ponce, Y. M.; Arán, Vicente J.; García-Trevijano, J. A. E.; Thu, H. L. T.; García Sánchez, Roy N.; Barrio, Alicia G.
    Increased efforts in antimalarial drug discovery are urgently needed. This paper applies a virtual screening protocol consisting of different computational filters in order to identify new antimalarial scaffolds from a structurally diverse library. This procedure has retained 38 new virtual hit which 12 were selected for experimental evaluation against Plasmodium falciparum, 3 of them showed significant antimalarial activity. These compounds have diverse chemical structures unrelated to existing antimalarial drugs can therefore be considered as new lead compounds, which leave an open door to the development of new antimalarials.

  19. Influence of protonation on the properties derived from electron density

    Alkorta, Ibon; Picazo, O.
    The effect of protonation on the electron density of a series of small molecules has been studied by means of the quantum theory of the Atoms in Molecules (QTAIM) methodology. The non-uniform redistribution of the electron density upon protonation of the systems produces an increase of the atomic energy of the protonated heteroatom and a reduction of the atomic charge for the protonated oxygen, while an increase of the charge on the protonated nitrogens is observed. The total volume of the protonated systems is smaller than that of the corresponding neutral ones. Thus, all the groups that form the molecule...

  20. The structure of 2,3-dihydro-3-(2,4-dioxo-6-methylpyran-3-ylidene)-2-(2- nitrobenzyl)-1,4-benzothiazine and the problem of orthogonal interactions

    Pinilla, Elena; Torres, M. D. R.; Claramunt, Rosa M.; Sanz, David; Prakash, R.; Singh, S. P.; Alkorta, Ibon; Elguero, José
    The structure of the title compound has been determined. The compound crystallizes in the P21/n space group with 4 molecules in the unit cell. The structure is consistent with previous conclusions based on NMR spectroscopy; moreover it provides new information about the conformation of the thiazine ring, the nature of the intramolecular hydrogen bond and the sulfur/nitro >orthogonal interaction>. This last aspect has been examined through the use of DFT calculations on a simplified model system. ©ARKAT.

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