This work aimed to develop a phosphorous-based biorefinery process for obtaining phosphorylated lignocellulosic fractions in a one-pot protocol from coconut fiber. Natural coconut fiber (NCF) was mixed with 85 % m/m H3PO4 at 70 °C for 1 h to yield the modified coconut fiber (MCF), aqueous phase (AP), and coconut fiber lignin (CFL). MCF was characterized by its TAPPI, FTIR, SEM, EDX, TGA, WCA, and P content. AP was characterized regarding its pH, conductivity, glucose, furfural, HMF, total sugars and ASL contents. CFL structure was evaluated by FTIR, 1H, 31P and 1H-13C HSQC NMR, TGA and P content and was compared to that of milled wood lignin (MWL). It was observed that MCF and CFL were phosphorylated during the pulping (0.54 and 0.23 % wt., respectively), while AP has shown high sugar levels, low inhibitor content, and some remaining phosphorous. The phosphorylation of MCF and CFL also showed an enhancement of their thermal and thermo-oxidative properties. The results show that a platform of functional materials such as biosorbents, biofuels, flame retardants, and biocomposites can be created through an eco-friendly, simple, fast, and novel biorefinery process.

There is a growing environmental concern in the world for replacing the traditional petroleum-based products. The aim of this work was to evaluate the structure – property relationship of banana peel lignins (BPLs) as antioxidant and antimicrobial agents by controlling the parameters of organosolv process. The milled banana peel was hydrolyzed using an aqueous acetic acid solution (70, 80 and 90% v/v) and 2.0% v/v HCl at 110 °C for 1, 2 and 3 h. BPLs were characterized by FTIR, 1H NMR, 1H13C HSQC, 31P NMR, GPC and TGA. The antioxidant capacity of BPLs was evaluated by DPPH, ABTS and H2O2 assays, comparing their performance with that of ascorbic and gallic acid. The antimicrobial activity of BPLs was evaluated against E. coli. The reaction time and acetic acid/water ratio had significant effects on the yield and purity of BPLs. The composition of organosolv solution also affected their total amount of hydroxyls (0.71–0.82 mmol g−1), Mw (2759–3954 g mol−1), Tonset (232–254 °C), antioxidant and antimicrobial activities. It can be concluded that the control of organosolv parameters can be a useful tool for tuning the structural features of lignins and to maximize their performance.

Microorganisms can produce a great variety of enzymes in short growing time, and their enzyme complexes have been used in multi-step bioconversions of natural products. Whole cells from different fungal strains were capable of biotransforming diterpenes through a variety of reactions, most of them involving enzymes that promote carbon oxidations. In this paper, we report the first biotransformation of the cytotoxic pimarane-type diterpene annonalide (1) into nor-annonalide (2) by growing cells of the filamentous fungus Fusarium oxysporum f. sp. tracheiphilum (UFCM 0089). Lipase, decarboxylase and alcohol dehydrogenase (ADH) enzymes mediated this unprecedented bioconversion. Theoretical studies (DFT analysis, molecular docking and molecular dynamics) were performed as an attempt to propose a plausive pathway involved on the formation of product 2, and binding interactions of intermediate 1a into the catalytic site of pyruvate decarboxylase enzyme were identified.

Abstract Introduction: In recent decades, several researches have been conducted in search of new analgesics that do not present the side effects of opioids. In this context, animal venoms contain natural painkillers that have been used for the development of new analgesics. Objective: The aims of this study were to evaluate the antinociceptive effects of telocinobufagin (TCB), a bufadienolide isolated from Rhinella jimi venom, in murine acute pain models, and to verify the participation of the opioid system in these effects. Methods: TCB was purified from R. jimi venom by high-performance liquid chromatography, and its structure was confirmed by spectrometric techniques. TCB was administered intraperitoneally (i.p.) (0.062, 0.125, 0.25, 0.5, and 1 mg·kg−1) and orally (p.o.) (0.625, 1.125, 2.5, 5, and 10 mg·kg−1) in mice, which were then subjected to pain tests: acetic acid–induced writhing, formalin, tail-flick, and hot-plate. Involvement of the opioid system in TCB action was evaluated by naloxone i.p. injected (2.5 mg·kg−1) 20 minutes before TCB administration. In addition, the TCB action on the μ, δ, and κ opioid receptors was performed by radioligand binding assays. Results: In all the tests used, TCB showed dose-dependent antinociceptive activity with more than 90% inhibition of the nociceptive responses at the doses of 1 mg·kg−1 (i.p.) and 10 mg·kg−1 (p.o.). Naloxone did not alter the effect of TCB. In addition, TCB did not act on the μ, δ, and κ opioid receptors. Conclusion: The results suggest that TCB may represent a novel potential nonopioid therapeutic analgesic for treatment of acute pains.

Cardiotonic steroids (CS) are known as modulators of sodium and water homeostasis. These compounds contribute to the excretion of sodium under overload conditions due to its natriuretic property related to the inhibition of the renal Na+/K+-ATPase (NKA) pump α1 isoform. NHE3, the main route for Na+ reabsorption in the proximal tubule, depends on the Na+ gradient generated by the NKA pump. In the present study we aimed to investigate the effects of marinobufagin (MBG) and telocinobufagin (TBG) on the renal function of isolated perfused rat kidney and on the inhibition of NKA activity. Furthermore, we investigated the mechanisms for the cardiotonic steroid-mediated natriuretic effect, by evaluating and comparing the effects of bufalin (BUF), ouabain (OUA), MBG and TBG on NHE3 activity in the renal proximal tubule in vivo. TBG significantly increased GFR, UF, natriuresis and kaliuresis in isolated perfused rat kidney, and inhibits the activity of NKA at a much higher rate than MBG. By stationary microperfusion technique, the perfusion with BUF, OUA, TBG or MBG promoted an inhibitory effect on NHE3 activity, whereas BUF was the most effective agent, and demonstrated a dose-dependent response, with maximal inhibition at 50nM. Furthermore, our data showed the role of NKA-Src kinase pathway in the inhibition of NHE3 by CS. Finally, a downstream step, MEK1/2-ERK1/2 was also investigated, and, similar to Src inhibition, the MEK1/2 inhibitor (U0126) suppressed the BUF effect. Our findings indicate the involvement of NKA-SRc-Kinase-Ras-Raf-ERK1/2 pathway in the downregulation of NHE3 by cardiotonic steroids in the renal proximal tubule, promoting a reduction of proximal sodium reabsorption and natriuresis.

Seven withanolides, including four previously unknown, were isolated from the acetone and ethanol extracts of cultivated specimens of Acnistus arborescens. These four compounds were identified as rel-(18R,22R)-5 beta,6 beta:18 beta,20-diepoxy-3 beta,18 alpha-dimethoxy-4 beta-hydroxy-1-oxowith-24-enolide, rel-(20R,22R)-5 beta,6 beta-epoxy-4 beta,16 alpha,20-trihydroxy-1-oxowitha-2,24dienolide, rel-(20R,22R)-16 alpha-acetoxy-6 alpha-chloro-4 beta,5 beta,20-trihydroxy-1-oxowitha-2,24-dienolide and rel-(20R,22R)-16 alpha-acetoxy-20-hydroxy-1-oxowitha-2,5,24-trienolide. Their structures were elucidated by interpretation of spectroscopic data (1D and 2D NMR), HRESIMS experiments and comparison with published data for similar compounds. Cytotoxicity of the isolated compounds was evaluated against a panel of four tumor cell lines (HL-60, HCT-116, SF-268 and PANC-1). Withanolide D was the most active, with an IC50 value in the range of 0.31.7 mu M, rel-(18R,22R)-5 beta,6 beta:18 beta,20-diepoxy-3 beta,18 alpha-dimethoxy-4 beta-hydroxy-1-oxowith-24-enolide and rel-(20R,22R)-5 beta,6 beta-epoxy-4 beta,16 alpha,20-trihydroxy-1-oxowitha-2,24dienolide were moderately active, while all the others were non-cytotoxic. (C) 2016 Elsevier Ltd. All rights reserved.

A competência para realização de auditorias operacionais (AOPs), importante instrumento de fiscalização do desempenho de órgãos e entidades governamentais e de políticas e programas públicos, fortaleceu o papel dos tribunais de contas (TCs) para a accountability, notadamente para a accountability por resultados. Porém, a realização de AOPs impõe desafios aos TCs, uma vez que, historicamente, exerciam prioritariamente a accountability de regularidade, ou seja, no exame do cumprimento de normas e de procedimentos, com a eventual responsabilização dos gestores em caso de irregularidade, em detrimento das AOPs, muito mais eficazes para a responsabilização no caso de irregularidades. A partir do estudo de caso de AOPs no âmbito do Tribunal de Contas do Estado de Minas Gerais (TCEMG), este artigo busca examinar as dificuldades para o desempenho de tais auditorias bem como os benefícios advindos de sua realização, de acordo com a percepção de atores do TCEMG e de representantes de órgãos ou entidades governamentais. Foram oito as auditorias selecionadas, do período de 2007 a 2012, abrangendo o exame do desempenho de determinada Secretaria de Estado quanto aos procedimentos de celebração de convênios com municípios mineiros; ao exame dos resultados de um programa de assistência jurídica da Defensoria Pública do Estado de Minas Gerais e aos programas relacionados a distintas áreas de atuação do governo estadual. O estudo coletou dados mediante aplicação de questionários, no período de outubro de 2013 a janeiro de 2014 — no âmbito interno do TCEMG — aos conselheiros, aos conselheiros substitutos e aos analistas da Coordenadoria de Auditoria Operacional, atores considerados estratégicos para a adoção e o aprimoramento das AOPs. E, no âmbito externo, a interlocutores dos órgãos ou entidades envolvidos nos programas auditados. Os resultados revelaram a necessidade de investimentos e de aprimoramentos para a execução das AOPs, tanto no que se refere aos auditores do TCEMG quanto aos órgãos e entidades submetidas a tais auditorias. Quanto aos auditados, o grande desafio, na realização das AOPs, é vencer a resistência e o receio quanto à possível repercussão política negativa das constatações das referidas auditorias. O desafio, em suma, consiste em considerar as AOPs ferramenta imprescindível de contribuição para a melhoria dos programas públicos e para a efetivação da accountability, tendo em vista a maior transparência da gestão pública e o fomento do controle social.

This paper describes the development and application of a new educational software. It is intended to support teachers and students in the teaching-learning process on chemical solutions, while helping them in daily basis lab calculations. By using animations, interactive calculations and simulations, this software offers an introduction and practice of many concepts on the chemistry of solutions, e.g. units of concentration, solution preparation and colligative properties. Additionally, it was evaluated by 102 undergraduate students which agreed that this software is a comprehensive and easy to use and should complement their textbooks.

Este artigo descreve o desenvolvimento e aplicacao de um novo software educacional que pretende auxiliar professores e estudantes no processo de ensino-aprendizagem de solucoes quimicas e tambem auxilia-los nos calculos realizados na rotina de laboratorio. O software introduz muitos conceitos da quimica de solucoes, tais como unidades de concentracao, preparacao de solucoes e propriedades coligativas, atraves de animacoes, calculos interativos e simulacoes. A avaliacao realizada por 102 estudantes de graduacao confirmou que este software tem um conteudo abrangente, de facil navegacao e deveria ser utilizado como ferramenta complementar dos livros-texto. DOI: 10.5935/1984-6835.20140059

Bufadienolides are structurally related to the clinically relevant cardenolides (e.g., digoxin) and are now considered as endogenous steroid hormones. Binding of ouabain to Na(+)-K(+)-ATPase has been associated, in kidney cells, to the activation of the Src kinase pathway and Na(+)-K(+)-ATPase internalization. Nevertheless, whether the activation of this cascade also occurs with other cardiotonic steroids and leads to diuresis and natriuresis in the isolated intact kidney is still unknown. In the present work, we perfused rat kidneys for 120 min with bufalin (1, 3, or 10 μM) and measured its vascular and tubular effects. Thereafter, we probed the effect of 10 μM 3-(4-chlorophenyl)1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4amine (PP2), a Src family kinase inhibitor, and 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (UO126), a highly selective inhibitor of both MEK1 and MEK2, on bufalin-induced renal alterations. Bufalin at 3 and 10 μM profoundly increased several parameters of renal function in a time- and/or concentration-dependent fashion. At a concentration that produced similar inhibition of the rat kidney Na(+)-K(+)-ATPase, ouabain had a much smaller diuretic and natriuretic effect. Although bufalin fully inhibited the rat kidney Na(+)-K(+)-ATPase in vitro, its IC(50) (33 ± 1 μM) was threefold higher than the concentration used ex vivo and all its renal effects were blunted by PP2 and UO126. Furthermore, the phosphorylated (activated) ERK1/2 expression was increased after bufalin perfusion and this effect was totally prevented after PP2 pretreatment. The present study shows for the first time the direct diuretic, natriuretic, and kaliuretic effects of bufalin in isolated rat kidney and the relevance of Na(+)-K(+)-ATPase-mediated signal transduction.

The organic extracts of leaves and roots of Psychotria stachyoides provided the new glucoside monoterpenoid indole alkaloid N-demethylcorreantoside, besides bizantionoside B, alpha-amyrin, alizarine methyl-ether, rubiadine, scopoletin, barbinevic acid and a mixture of beta-sitosterol and stigmasterol glucosides. The structural characterization of the isolates was established based on infrared spectroscopy (IR), mass spectrometry (MS) and, particularly, 1D and 2D nuclear magnetic resonance (NMR).

Compounds with dual action on cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) may be a treatment option for erectile dysfunction, as they not only promote penile erection but also prevent the upregulation of phosphodiesterase-5. In this study, we examined the possible relaxant effect and mechanism of 17-nor-subincanadine E (SEC, 0.2-200 mu mol l(-1)), a plant-derived alkaloid, in rabbit corpus cavernosum (RbCC) strips that had been precontracted by exposure to phenylephrine (10 mu mol l(-1)) or a high concentration of K+ (60 mmol l(-1)) in vitro. In addition to SEC's effect on cAMP and cGMP levels, electrical field stimulation (EFS) in phenylephrine-precontracted RbCC and calcium chloride (1-100 mmol l(-1)) evoked responses in depolarized RbCC were analysed. SEC relaxed the phenylephrine-precontracted RbCCs in a concentration-dependent manner. Atropine, guanethidine and N-omega-nitro-L-arginine methyl ester (L-NAME) did not have any effect on the relaxation of RBCCs. When 1H-(1,2,4)oxadiazole[4,3-a] quinoxalin-1-one (ODQ) was added, it effectively blocked the relaxant response of SEC. Although SEC enhanced the maximal relaxation produced by sodium nitroprusside (SNP) and forskolin in phenylephrine-precontracted cavernosal smooth muscle, it caused a decrease in the maximal contractile response induced by calcium chloride in depolarized RbCCs. The relaxant effect of SEC was paralleled by an increase in the tissue levels of the cyclic nucleotides cAMP and cGMP. We conclude that SEC promotes the relaxation of RbCC, possibly favouring cAMP and cGMP accumulation and calcium blockade. This novel mechanism could be useful for patients who do not benefit from phosphodiesterase inhibitors and for those with endothelial and nitrergic dysfunction, such as patients with diabetes, hypertension and dyslipidaemias. Asian Journal of Andrology (2011) 13, 747-753; doi:10.1038/aja.2011.41; published online 18 July 2011

1H and 13C NMR chemical shifts of praecansone B, pongaflavone and dehydrorotenone isolated from Tephrosia egregia Sandw and obovatin from T. toxicaria Pers. were unambiguously assigned by 1D and 2D NMR experiments including 1H, 1H COSY, gHMQC and gHMBC, allowing the correction of literature assignments.Copyright © 2009 John Wiley & Sons, Ltd.

Two novel indole alkaloids with plumeran skeleton, spruceanumines A (1) and B (2), and eight known indole alkaloids, aspidospermidine (3), demethoxypalosine (4), aspidocarpine (5), aspidolimine (6), fendlerine (7), aspidolimidine (8), obscurinervidine (9) and obscurinervine (10) were isolated from stem bark and seeds methanolic extracts of Aspidosperma spruceanum. Compounds structures were elucidated on the basis of spectroscopic data, mainly those obtained by H-1 and C-13 NMR (1D and 2D) and mass spectrometry.

We described earlier that an alkaloid-rich fraction (F3–5) from Aspidosperma ulei (Markgr) induces penile erection-like behavioral responses in mice. This study verified a possible relaxant effect of this fraction on isolated rabbit corpus cavernosum (RbCC) strips precontracted by phenylephrine (1 μM) or K+ 60 mM. F3–5 (1–300 μg ml−1) relaxed the RbCC strips in a concentration-dependent and reversible manner. The relaxant effect of F3–5 (100 μg ml−1) on phenylephrine contraction was unaffected in the presence of atropine, N-ω-nitro-L-arginine methyl ester or 1H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1-one and by preincubation with tetrodotoxin, glibenclamide, apamine and charybdotoxin suggesting that mechanisms other than cholinergic, nitrergic, sGC activation or potassium channel opening are probably involved. However, the phasic component of the contraction induced by K+ 60 mM as well as the maximal contraction elicited by increasing external Ca2+ concentrations in depolarized corpora cavernosa was inhibited by F3–5. We conclude that F3–5 relaxes the RbCC smooth muscle, at least in part, through a blockade of calcium influx or its function.

The distribution of iridoid glucosides in plants from the genus Lippia (Verbenaceae) is described. In the present work, three known iridoids (theviridoside, mussaenoside and gardoside) were isolated from the roots of L. alba and were confirmed by NMR (1H and 13C) spectroscopic data. This information was combined with previous work on seven other Lippia species (obtained through a literature review) to give a thorough account of the iridoid glucosides currently found in this genus.