Synthesis of chromone-related pyrazole compounds

Chromones, six-membered oxygen heterocycles, and pyrazoles, five-membered two-adjacent-nitrogen-containing heterocycles, represent two important classes of biologically active compounds. Certain derivatives of these scaffolds play an important role in medicinal chemistry and have been extensively used as versatile building blocks in organic synthesis. In this context, we will discuss the most relevant advances on the chemistry that involves both chromone and pyrazole rings. The methods reviewed include the synthesis of chromone-pyrazole dyads, synthesis of chromone-pyrazole-fused compounds, and chromones as starting materials in the synthesis of 3(5)-(2-hydroxyaryl)pyrazoles, among others. This review will cover the literature on the chromone and pyrazole dual chemistry and their outcomes in the 21st century.Thanks are due to University of Aveiro and FCT/MEC for the financial support of the QOPNA research unit (FCT UID/QUI/00062/2013) and CIQ-UP, University of Porto (POCI-01-0145-FEDER-006980; FCT: UID/QUI/00081/2013) through national founds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement, as well as to the Polytechnic Institute of Bragança. V.L.M.S. is grateful to FCT for her grant (SFRH/BPD/108807/2015), in the ambit of “QREN e POCH e Tipologia 4.1 e Formação Avançada”, co-sponsored by FSE and by national funds of MCTES.info:eu-repo/semantics/publishedVersio

Arylxanthones and arylacridones: a synthetic overview

Arylxanthones and arylacridones although not yet found in nature are becoming an important group of heterocyclic compounds due to their promising biological activities. Their central cores, xanthone and acridone, are recognized as interesting motifs for drug development mainly to be used in antitumour chemotherapy. The synthesis of this type of compounds is still scarce but several successful examples were recently published and a large variety of arylated xanthone and acridone derivatives were prepared. A systematic survey of the literature dedicated to their synthesis will be presented and discussed in this review.Thanks are due to the University of Aveiro, Polytechnic Institute of Bragança, Fundação para a Ciência e a Tecnologia (FCT) FCT/MEC for the financial support of the QOPNA research Unit (FCT UID/QUI/00062/2013) through national founds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement. V.L.M. Silva also acknowledges FCT for the financial support of her post-doctoral grant (SFRH/BPD/108807/2015), in the ambit of “QREN e POCH e Tipologia 4.1 e Formação Avançada”, co-sponsored by FSE and by national funds of MCTESinfo:eu-repo/semantics/publishedVersio

MS-222 toxicity in juvenile seabream correlates with diurnal activity, as measured by a novel video-tracking method

©2010. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in Aquaculture. To access the final edited and published work see https://doi.org/10.1016/j.aquaculture.2010.06.028Fish are frequently exposed to anaesthetics since their use is necessary in several aquaculture procedures. The aim of this study was to investigate the existence of day night differences in toxicity and effectiveness of a common fish anaesthetic (MS-222) in juvenile gilthead seabream (Sparus aurata), determining the induction time of anaesthesia and subsequent recovery by a novel video-recording system. Our results showed that MS-222 toxicity was significantly higher at ML (mid-light) (LC50=85.5 mg/L) than at MD (mid-darkness) (LC50=107.6 mg/L) (trimmed Spearman-Karber method). In addition, when fish were exposed to a sublethal but effective MS-222 concentration (65 mg/L), 7 min passed before 50% a reduction in swimming activity was observed at ML compared to the 9 min required at MD. As regards recovery, fish showed activity levels similar to basal levels 10 min after MS-222 removal at ML, but only 6 min at MD. These results indicated that both toxicity and effectiveness were higher during the day than at night, coinciding with the diurnal activity pattern displayed by seabream, which should be taken into account when designing and applying daily protocols for anaesthesia in aquacultur

Influence of light intensity on plasma melatonin and locomotor activity rhythms in tench

©2005. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in Chronobiology International: The Journal of Biological and Medical Rhythm Research.Melatonin production by the pineal organ is influenced by light intensity, as has been described in most vertebrate species, in which melatonin is considered a synchronizer of circadian rhythms. In the case of tench, strict nocturnal activity rhythms have been described although the role of melatonin has not been clarified. In this study we investigated daily activity and melatonin rhythms under 12:12 light-dark (LD) conditions with two different light intensities (58.6 and 1091µW/cm2 ), and the effect of one hour broad spectrum white light pulses of different intensities (3.3, 5.3, 10.5, 1091.4 µW/cm2 ) applied at mid darkness (MD) on nocturnal circulating melatonin. The results showed that plasma melatonin in tench under LD 12:12 and high light conditions displayed a rhythmic variation, where values at MD (255.8 ± 65.9 pg/ml) were higher than at mid light (ML) (70.7 ± 31.9 pg/ml). Such a difference between MD and ML values was reduced in animals exposed to LD 12:12 and low light intensity. The application of one hour light pulses at MD lowered plasma melatonin to 111.6 ± 3.2 pg/ml (in the 3.3-10.5 µW/cm2 range) and to 61.8 ± 18.3 pg/ml (with the 1091.4 µW/cm2 light pulse) and totally suppressed nocturnal locomotor activity. These results showed that melatonin rhythms persisted in tench exposed to low light intensity although the amplitude of the rhythm is affected. In addition, it was observed that light pulses applied at MD affected plasma melatonin content and locomotor activity. Such a low threshold suggests that the melatonin system is capable of transducing light even under dim conditions, which may be used by this nocturnal fish to synchronize to weak night light signals (e.g. moonlight cycles

Feeding entrainment of locomotor activity rhythms, digestive enzymes and neuroendocrine factors in goldfish

©2007. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in Journal of PHYSIOL BEHAV. To access the final edited and published work see http://doi: 10.1016/j.physbeh.2006.10.017L.M. VERA, N. DE PEDRO, E. GÓMEZ-MILÁN, M.J. DELGADO, M.J. SÁNCHEZ MUROS, J.A. MADRID, F.J. SÁNCHEZ-VÁZQUEZ. Feeding entrainment of locomotor activity, digestive enzymes and neuroendocrine factors in goldfish. PHYSIOL BEHAV 90 (2-3) 518-524, 2007. The existence of food anticipatory activity (FAA) in animals subjected to daily feeding schedules seems to be mediated by a feeding-entrainable oscillator (FEO). Such an FEO may help in anticipating meal time and so optimizing food acquisition and nutrient utilization. In this study we investigated the existence of FAA and whether digestive enzymes, plasma cortisol, hypothalamic NPY and gastrointestinal tract (GIT) and plasma melatonin were entrained by periodic feeding in goldfish. We observed that periodically fed goldfish showed FAA in locomotor activity as well as in amylase and NPY. Alkaline protease and GIT melatonin were higher after feeding, whereas plasma cortisol levels were reduced. Plasma melatonin remained unmodified before and after meal time. These results suggested that scheduled feeding entrained both behavioral and certain physiological patterns in goldfish, FAA being of adaptive value to anticipate a meal and prepare the digestive physiology of fish

A study towards drug discovery for the management of type 2 diabetes: Mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives

The inhibition of carbohydrate-hydrolyzing enzymes, α-amylase and α-glucosidase, is one of the major therapeutic strategies for the treatment of type 2 diabetes mellitus. Chalcones have been recognized for their multiple biological activities, including antidiabetic properties, through unclear mechanisms. In the present work, a panel of chalcones bearing hydroxy, methoxy, methyl, nitro, chloro, fluoro and bromo substituents were evaluated against α-amylase and α-glucosidase activities, most of them for the first time. The results showed that the substitution patterns and the type of substituents of chalcones influence their inhibitory activity. The presence of hydroxy groups at C-2’- and C-4’ of the A ring and at C-3 and C-4 of the B ring favors the intended effect. Chalcones holding nitro groups and chloro substituents, together with a hydroxy group in the chalcone scaffold, showed strong inhibition of the α-glucosidase activity. The present study provides related scaffolds that may serve as the basis for the design and synthesis of new structures in order to obtain the ideal antidiabetic chalcone.This work received financial support from the European Union (FEDER funds POCI/01/0145/FEDER/007265) and National Funds (FCT/MEC, Fundação para a Ciência e Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/QUI/50006/2013, and “Programa Operacional Competitividade e Internacionalização” (COMPETE) (POCI-01-0145-FEDER-029241). Thanks are due to University of Aveiro, Instituto Politécnico de Bragança, FCT/ MEC for the financial support to the QOPNA (FCT UID/QUI/ 00062/2013) and CIMO (UID/AGR/00690/2013) research Units through national funds and where applicable co-financed by the FEDER, within the PT2020 Partnership Agreement, and also to the Portuguese NMR Network. Sónia Rocha acknowledges FCT the financial support for the PhD grant (PD/BD/ 145169/2019), in the ambit of “QREN – POPH – Tipologia 4.1 – Formação Avançada”, co-sponsored by Fundo Social Europeu (FSE) and by national funds of Ministério da Ciência, Tecnologia e Ensino Superior (MCTES).info:eu-repo/semantics/publishedVersio

The Impact of Stellar Migration on Disk Outskirts

Stellar migration, whether due to trapping by transient spirals (churning), or to scattering by non-axisymmetric perturbations, has been proposed to explain the presence of stars in outer disks. After a review of the basic theory, we present compelling, but not yet conclusive, evidence that churning has been important in the outer disks of galaxies with type II (down-bending) profiles, while scattering has produced the outer disks of type III (up-bending) galaxies. In contrast, field galaxies with type I (pure exponential) profiles appear to not have experienced substantial migration. We conclude by suggesting work that would improve our understanding of the origin of outer disks.Comment: Invited review, Book chapter in "Outskirts of Galaxies", Eds. J. H. Knapen, J. C. Lee and A. Gil de Paz, Astrophysics and Space Science Library, Springer, in press 39 pages, 15 figure

Effects of long-term diet supplementation with Gliricidia sepium foliage mixed with Enterolobium cyclocarpum pods on enteric methane, apparent digestibility, and rumen microbial population in crossbred heifers

In the last decades, strategies have been evaluated to reduce rumen methane (CH4) production by supplementing tropical forages rich in secondary compounds; however, most of these beneficial effects need to be validated in terms of their persistence over time. The aim of this study was to assess CH4 emissions over time in heifers fed with and without Gliricidia sepium foliage (G) mixed with ground pods of Enterolobium cyclocarpum(E). Two groups of four crossbred (Bos taurus x Bos indicus) heifers (284 ±17 kg initial weight) were fed with two diets (0 and 15% of a mixture of the pods and foliage [E+G:0 and E+G:15, respectively] over 80 days, plus two weeks before the experiment, in which every animal was fed a legume and pod-free diet. Every 14 days, CH4 production, apparent digestibility, volatile fatty acids (VFA), and microbial population were quantified for each animal. The experiment was conducted with a repeated measurements design over time. Diets fed differed in terms of their crude protein (CP), condensed tannins (CT) and saponins content supplied by E. cyclocarpum and G. sepium. For most of the experiment, dry matter intake (DMI) and digestible dry-matter intake (DDMI) were 6.3 kg DMI/d and 512 g DDMI/kg, respectively for both diets (Diet: P>0.05). Apparent digestible crude protein (DCP) was reduced by 21 g DCP/kg DM when the diet was supplemented with E+G:15 (P=0.040). Molar proportions of VFA’s in the rumen did not differ between diets or in time (P>0.05). Daily methane production, expressed in relation to DMI was 23.95 vs 23.32 g CH4/kg DMI for the diet E+G:0 and E+G:15 respectively (Diet: P=0.016; Time: P>0.05). Percent gross energy loss as CH4 (Ym) with grassonly diets was above 8.1%, whereas when feeding heifers with the alternate supplementation, Ym values of 7.59% (P=0.016) were observed. The relative abundance of total bacterial, protozoa, and methanogenic archaeal replicates was not affected by time nor by the incorporation of legume and pods into the diet (P>0.05). Results suggest that addition of G. sepium mixed with E. cyclocarpum pods can reduce CH4 production in heifers and this response remains over time, without effect on microbial population and VFA concentration and a slight reduction in crude protein digestibility

Vírus da encefalite São Luis: primeiro isolamento de humano no Estado de São Paulo, Brasil

O presente estudo relata o isolamento do vírus da encefalite São Luis (SLEV) de um caso febril humano suspeito de dengue, em São Pedro, Estado de São Paulo. MAC-ELISA realizado com soros das fases aguda e convalescente foi inconclusivo e anticorpos IgG foram detectados por inibição da hemaglutinação para flavivirus. Imunofluorescência indireta com cultura de células C6/36 inoculadas com soro da fase aguda foi positivo para flavivirus mas negativo quando testado com anticorpos monoclonais para dengue. O RNA extraído de cultura de células infectadas foi amplificado na presença de primers universais para o gênero Flavivirus, deduzidos de uma região da proteína não estrutural 5 e diretamente sequenciado. Os resultados da pesquisa no BLAST indicaram que a seqüência apresenta 93% de similaridade de nucleotídeos com a seqüência de SLEV (cepa MS1.7), confirmado por RT-PCR, realizado com primers específicos para SLEV. O fato de SLEV ter sido identificado como a causa de doença humana indica a necessidade de aprimorar a vigilância a fim de detectar precocemente esse agente no Estado de São Paulo e no Brasil. Esse caso é também um alerta para os profissionais de saúde sobre a necessidade de investigações clínicas e epidemiológicas mais completas sobre doenças febris como no caso relatado. Infecções por SLEV podem não ser reconhecidas ou confundidas com outras causadas por arbovírus como a dengue.This paper reports the isolation of St. Louis encephalitis virus (SLEV) from a febrile human case suspected to be dengue, in São Pedro, São Paulo State. A MAC-ELISA done on the patient's acute and convalescent sera was inconclusive and hemagglutination inhibition test detected IgG antibody for flaviviruses. An indirect immunofluorescent assay done on the C6/36 cell culture inoculated with the acute serum was positive for flaviviruses but negative when tested with dengue monoclonal antibodies. RNA extracted from the infected cell culture supernatant was amplified by RT-PCR in the presence of NS5 universal flavivirus primers and directly sequenced. Results of BLAST search indicated that this sequence shares 93% nucleotide similarity with the sequence of SLEV (strain-MSI.7), confirmed by RT-PCR performed with SLEV specific primers. Since SLEV was identified as the cause of human disease, it is necessary to improve surveillance in order to achieve early detection of this agent in the state of São Paulo and in Brazil. This finding is also an alert to health professionals about the need for more complete clinical and epidemiological investigations of febrile illnesses as in the reported case. SLEV infections can be unrecognized or confused with other ones caused by an arbovirus, such as dengue