NEW BUTYROLACTONE FROM A MARINE-DERIVED FUNGUS ASPERGILLUS SP

Indexación: Web of Science; ScieloFour compounds that belong to two structure types, namely dibenzylbutyrolactone and sesterterpenoids, were obtained from the extract of the strain Aspergillus sp. (2P-22), isolated from a marine sponge, Cliona chilensis. Among them, compound 1 was identified as new, namely butylrolactone-VI. The structures of these compounds were characterized on the basis of spectroscopic data. Biological activities of these fungal metabolites, are described.http://ref.scielo.org/kbf7v

Corpus documental de las Islas Canarias: un nuevo reto en humanidades digitales

Internet nos brinda la oportunidad de traspasar fronteras y de acortar las distancias del aislamiento de los archivos insulares, al tiempo que nos permite ofrecer un conjunto textual, amplio y suficientemente representativo, que facilite la consulta de la documentación isleña y la comparación con otros corpus similares de otras regiones. Con este objetivo hemos trabajado durante los últimos años en la transcripción de cientos de documentos con el fin de iniciar la elaboración de un corpus modular diatópico de pequeño dominio, perfectamente datado y etiquetado. En este artículo presentaremos los aspectos más destacados de este inventario documental, la procedencia y tipología de los registros, los criterios de transcripción utilizados, la acotación temporal y los metadatos que facilitarán los parámetros de búsquedaThe internet offers the opportunity of going beyond borders, apart from reducing the isolation of the island archives. At the same time, it allows us to offer an extensive and sufficiently representative set of texts, which facilitates the consultation of the island documentation and enables us to compare it with similar corpora from other regions. For this purpose, we have been working on the transcriptions of hundreds of documents over the last years in order to begin the elaboration of a modular diatopic corpus of small domain, which is perfectly dated and tagged. In this paper, we will present the main aspects of this documentary inventory, the origin and the typology of the documents, the criteria employed in the transcription, the time frame and the metadata, which will facilitate the search parameter

8-Propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one: A new coumarin with monoamine oxidase B inhibitory activity and possible anti-parkinsonian effects

Parkinson’s disease is a common neurodegenerative disorder. In this study, the monoamine oxidase inhibitory activity and potential anti-parkinsonian effects of 8-propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one (FCS303), a new synthetic coumarin, were evaluated. To do this, we used the reserpine model of Parkinson’s disease, an assay of levodopa/carbidopa potentiation, the catalepsy model of haloperidol, and an in vitro assay against monoamine oxidase (MAO) activity. Additionally, lipid peroxidation and protein carbonyl group quantification was performed in mice brain homogenates previously treated with haloperidol. FCS303 inhibited monoamine oxidase B (MAO-B) with an IC50 of 5.46 ± 0.36 µM; however, there was no effect on monoamine oxidase A (MAO-A). The oral administration of FCS303 led to a significant reversal of hypokinesia in the reserpine model (at 24 h, doses of 100 and 200 mg/kg) and in the levodopa/carbidopa potentiation assay (at 2 and 24 h, dose of 200 mg/kg). In addition, FCS303 (100 mg/kg) showed anti-cataleptic activity against haloperidol. FCS303 (50 mg/kg) significantly decreased lipid peroxidation and protein carbonyl quantification. These results suggest that FCS303 could present anti-parkinsonian activity related to MAO-B inhibitory activity.This work was conducted with funding from Universidad Nacional de Colombia, Bogotá (VRI/DIB, Project: 13668)S

QSAR for Anti-RNA-Virus Activity, Synthesis, and Assay of Anti-RSV Carbonucleosides Given an Unify Representation of Spectraö Moments, Quadratic, and Topologic Indices

The 9th International Electronic Conference on Synthetic Organic Chemistry session Computational ChemistryThe unify representation of spectral moments, classic topologic indices, quadratic indices, and stochastic molecular descriptors shown that all these molecular descriptors lie within the same family. Consequently, the same priori probability for a success quantitative-structure-activity-relationship (QSAR) may be expected no matter which indices are selected. Herein, we used stochastic spectral moments as molecular descriptors to seek a QSAR using a database of 221 bioactive compounds previously tested against diverse RNA-viruses and 402 non-active ones. The QSAR model thus obtained correctly classifies 90.9 % of compounds in training. The model also correctly classifies a total of 87.9 % of 207 compounds on additional external predicting series, 73 of them having anti-RNA-virus activity and 134 non-active ones. In addition, all compounds were regrouped into five different subsets for leave-group-out studies: 1) antiinfluenza, 2) anti-picornavirus, 3) anti-paramyxovirus, 4) anti-RSV/anti-influenza, and 5) broad range anti-RNA-virus activity. The model has retained overall accuracies about 90 % on these studies validating model robustness. Finally, we exemplify the practical use of the model with the discovery of compounds 124 and 128. These compounds presented MIC50 values = 3.2 and 8 µg/mL against respiratory syncytial virus (RSV) respectively. Both compounds have also low cytotoxicity expressed by their Minimal Cytotoxic Concetrations > 400 µg/mL for HeLa cells. The present approach represent and effort toward a formalization and application of molecular indices in bioinformatics, bioorganic and medicinal chemistryAuthors would like to express their gratitude by partial financial support to the Department of Organic Chemistry, University of Santiago de Compostel

Synthesis of new phthalazinedione derivatives

The 15th International Electronic Conference on Synthetic Organic Chemistry session General Organic SynthesisIn the past few decades, the synthesis of new heterocyclic compounds has been a subject of great interest due to their wide applicability. Among a large variety of heterocyclic compounds, heterocycles containing phthalazine moiety were reported to possess anticonvulsant, cardiotonic, and vasorelaxant activities. Therefore, a number of methods have been reported for the synthesis of phthalazine derivatives. Despite the available methods, the development of new synthetic methods for the efficient preparation of heterocycles containing phthalazine ring fragment is therefore an interesting challenge. With these precedents and with the aim of preparing new derivatives with potential pharmacological activity, we have synthesized new phthalazinedione derivatives by introducing halogenoalkyl substituents in one of the NH-nucleophilic groups. So, we started with 4-chloro-phthalic anhydride, which reacted with methyl- hydrazine, in MW mild conditions. After purification, we obtained two different isomers of phthalizediones, 8-chloro-2-methyl-2, 3-dihydro-phthalazine-1, 4-dione and 8-chloro-3-methyl-2, 3-dihydro-phthalazine-1,4-dione. Then halogenoalkyl substituents with different chain length were introduced in the nitrogen group in a very efficient way. Finally halogen atom of alkyl chains was replaced by an azide group. The described synthetic route will allow us to condense a nitrogen heterocyclic ring on the phatalazinone moiety and obtain a new tricyclic scaffold with promising pharmacological propertie

A reattributional training program as a therapeutic strategy for fear of flying

In this study the results for the validation of a reattributional training program applied to the fear of #ying are presented. The program is made up of 13 ($1) sessions and consists of three phases: Information; reattributional training; and the elaboration and application of the treatment designed by the patient with the help of the therapist. The program was applied to 24 patients while 24 other patients made up the waiting control group. The therapeutic success was evaluated by means of self-report scales, and by recording psychophysiological variables in a situation in which subjects viewed a video tape of a #ight. Signi"cant di!erences were obtained from the ANOVAs between experimental and control groups in all of the self-reported variables (p(0.001) and in some of the psychophysiological variables (p(0.05). The results support the e!ectiveness of the program. ( 2000 Elsevier Science Ltd. All rights reserved

Computational Drug Target Screening through Protein Interaction Profiles

The development of computational methods to discover novel drug-target interactions on a large scale is of great interest. We propose a new method for virtual screening based on protein interaction profile similarity to discover new targets for molecules, including existing drugs. We calculated Target Interaction Profile Fingerprints (TIPFs) based on ChEMBL database to evaluate drug similarity and generated new putative compound-target candidates from the non-intersecting targets in each pair of compounds. A set of drugs was further studied in monoamine oxidase B (MAO-B) and cyclooxygenase-1 (COX-1) enzyme through molecular docking and experimental assays. The drug ethoxzolamide and the natural compound piperlongumine, present in Piper longum L, showed hMAO-B activity with IC50 values of 25 and 65μM respectively. Five candidates, including lapatinib, SB-202190, RO-316233, GW786460X and indirubin-3′-monoxime were tested against human COX-1. Compounds SB-202190 and RO-316233 showed a IC50 in hCOX-1 of 24 and 25μM respectively (similar range as potent inhibitors such as diclofenac and indomethacin in the same experimental conditions). Lapatinib and indirubin3′-monoxime showed moderate hCOX-1 activity (19.5% and 28% of enzyme inhibition at 25μM respectively). Our modeling constitutes a multi-target predictor for large scale virtual screening with potential in lead discovery, repositioning and drug safetyThis study was supported by grant R01 LM006910 (GH) “Discovering and Applying Knowledge in Clinical Databases” from the U.S. National Library of Medicine, “Angeles Alvariño, Plan Galego de Investigación, Innovación e Crecemento 2011–2015 (I2C)” and European Social Fund (ESF)S

Antitumor activity of copper(II) complexes with Schiff bases derived from N′-tosylbenzene-1,2-diamine

The electrochemical oxidation of anodic metal copper in a solution of the ligands N-[(5-tert-butyl-2-hydroxyphenyl)methylidine]-N′-tosylbenzene-1,2-diamine [H2L1] and N-[(3,5-di-tert-butyl-2-hydroxyphenyl)methylidine]-N′-tosylbenzene-1,2-diamine, [H2L2] afforded homoleptic [CuL] compounds or solvate [CuLS] complexes. The addition to the electrochemical cell of coligands (L') such as 2,2′-bipyridine (2-bpy), 4,4′-bipyridine(4-bpy) or 1,10-phenanthroline (phen) allowed the synthesis, in one step, of heteroleptic [CuLL'] compounds, namely [CuL1(H2O)] (1), [CuL1(2,2′-bpy)]⋅CH3CN (2), [CuL1(phen)]·H2O (3), [Cu2L12(4,4′-bpy)] (4), [CuL2(CH3OH)] (5), [CuL2(2,2′-bpy)] (6), [CuL2(phen)] (7) and [Cu2L22(4,4′-bpy)] (8). The crystal structures of both ligands, H2L1, H2L2, and those of the complexes (2), (4), (5), (6) and (7) have been determined by X-ray diffraction techniques. Coordination polyhedron around metal atom is square planar for [CuL2(CH3OH)] (5) and [Cu2L12(4,4′-bpy)] (4) and square pyramid for the other complexes with additional chelating ligands. The cytotoxic activity of this new series of copper(II) complexes against the SH-SY5Y neuroblastoma cell line and U87-MG and U373-MG glioblastoma cell lines has been investigated. Most of the test compounds showed higher activity than cisplatin in the three cell lines. Among this series, compound [CuL1(phen)] (3) displayed the highest activity with IC50 equal to 1.77 μM on SH-SY5Y whereas compound [Cu2L12(4.4′-bpy)] (4) resulted the most potent compounds on U87 MG and U373 MG glioblastoma cell lines. Studies on the cytotoxic activity of these derivatives suggest that these compounds induce cell death by a mechanism other than apoptosis.Xunta de GaliciaFinanciado para publicación en acceso aberto: Universidade de Vigo/CISU

New cinnamic – N-benzylpiperidine and cinnamic – N,N-dibenzyl(N-methyl)amine hybrids as Alzheimer-directed multitarget drugs with antioxidant, cholinergic, neuroprotective and neurogenic properties

Here we describe new families of multi-target directed ligands obtained by linking antioxidant cinnamic-related structures with N-benzylpiperidine (NBP) or N,N-dibenzyl(N-methyl)amine (DBMA) fragments. Resulting hybrids, in addition to their antioxidant and neuroprotective properties against mitochondrial oxidative stress, are active at relevant molecular targets in Alzheimer’s disease, such as cholinesterases (hAChE and hBuChE) and monoamine oxidases (hMAO-A and hMAO-B). Hybrids derived from umbellic – NBP (8), caffeic – NBP (9), and ferulic – DBMA (12) displayed balanced biological profiles, with IC50s in the low-micromolar and submicromolar range for hChEs and hMAOs, and an antioxidant potency comparable to vitamin E. Moreover, the caffeic – NBP hybrid 9 is able to improve the differentiation of adult SGZ-derived neural stem cells into a neuronal phenotype in vitro.Financial support from the Spanish Ministry of Economy and Competitiveness (MINECO, grants SAF2012-31035 and SAF2015-64948-C2-1-R to MIRF; grant SAF2014-52940-R to APC) partially financed by FEDER funds, and Consejo Superior de Investigaciones Científicas (CSIC, grant PIE-201580E109) is gratefully acknowledged. ME thanks COLCIENCIAS (Colombia) for a Ph.D. fellowship.Peer reviewe

Benzopyran-2-ones as attractive scaffold for MAO inhibitors: synthesis, biological evaluation and docking studies

The 15th International Electronic Conference on Synthetic Organic Chemistry session Bioorganic, Medicinal and Natural ProductsNeurodegenerative diseases are becoming prevalent pathologies in developed societies due to increasing average of life expectancy of the population. This fact has encouraged an active research in the development of new drugs, since they may represent an important advance in the treatment of complex diseases such as Alzheimer and Parkinson\'s diseases. Coumarins are a large family of compounds, of both natural and synthetic origin, important because of the pharmacological activities that this compounds display. Therefore, they occupy an important place in the organic and medicinal chemistry realm. In recent years, coumarins have been attracting interest because of their ability of inhibiting some enzymes. The versatility of the Perkin and Knoevenagel reactions has led to a large family of differently substituted compounds. In order to find the structural features for the human MAO inhibitory activity and selectivity, in the present communication we report the synthesis, pharmacological evaluation and a comparative study of a new series of 3-phenylcoumarins versus 3-benzoylcoumarins. A bromo atom and a methoxy/hydroxy substituent were introduced in these scaffolds at different positions of the coumarin moiety. The synthesized compounds were evaluated as MAO-A and B inhibitors using R-(-)-deprenyl and iproniazide as reference compounds. The presence or absence of a carbonyl group between the coumarin and the phenyl substituent in 3 position remarks, respectively, the MAO-A or MAO-B inhibitory activity. Some of the new compounds showed MAO-B inhibitory activities in the low nanomolar range. Compound 2 (IC50 = 1.35 nM) showed higher inhibitory activity than the R-(-)-deprenyl (IC50 = 19.60 nM) and higher MAO-B selectivity, with more than 74,074-fold inhibition level, respecting to the MAO-A isoform. In addition, docking experiments were carried out on hMAO-A and h-MAO-B structures. This study has provided new information about the enzyme-inhibitor interaction and the potential therapeutic application of this coumarin scaffoldsThanks to the Ministerio Español se Sanidad Y Consumo (PS09/00501) and to Xunta de Galicia (PGIDIT09CSA030203PR and 10PXIB203303PR). S.V.R. thanks to Ministerio de Educación y Ciencia for a PhD grant (AP2008-04263). M.J.M. thanks Fundação para a Ciência e Tecnologia for a PhD grant (SFRH/BD/61262/2009)