Anticholinesterase activity evaluation of alkaloids and coumarin from stems of Conchocarpus fontanesianus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conchocarpus fontanesianus (A. St.-Hill.) Kallunki & Pirani, Rutaceae, popularly known as pitaguara, is a native and endemic tree from Sao Paulo and Rio de Janeiro States, Brazil. Based in the information that anticholinesterasic derivatives could act as new prototypes to treatment of Alzheimer disease, this work describes the fractionation guided by evaluation of the anticholinesterase activity of the ethanolic stems extract from C. fontanesianus. This procedure afforded the alkaloids dictamnine (1), gamma-fagarine (2), skimianine (3), and 2-phenyl-1-methyl-4-quinolone (4), as well as the coumarin marmesin (5).222374380Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Application of an Ionic Liquid in the Microwave Assisted Extraction of Cytotoxic Metabolites from Fruits of Schinus terebinthifolius Raddi (Anacardiaceae)

This work reports the application of an ionic liquid (1-butyl-3-methylimidazolium bromide, BMImBr) in the microwave assisted extraction (MAE) of metabolites from fruits of Schinus terebinthifolius. Dried fruits were individually extracted using BMImBr: H2O 1: 1, v/v (experiment 1) and pure H2O (experiment 2) by MAE (10 min at 60 degrees C). After partition using EtOAc, the yield to experiment 1 was about 23% while to experiment 2 was 0.1%. The EtOAc fraction obtained from experiment 1 was purified by chromatographic methods to afford 3-oxotirucalla-7,24Z-dien27- oic acid, 3a-hydroxytirucalla-7,24Z-dien-27-oic acid, 3 alpha-acetoxytirucalla-7,24Z-dien-27-oic acid, gallic acid, and ethyl gallate, being the first occurrence of the third compound as natural product. Cytotoxic activity was evaluated in vitro against cancer cell lines (A2058, HeLa, SiHa, HCT, SKBR-3, U87, and B16F2Nex2), being 3 alpha-acetoxytirucalla-7,24Z-dien-27-oic acid the more active metabolite with IC50 ranging from 10.9 +/- 1.3 to 17.3 +/- 1.4 mu g mL(-1), lower than that determined to positive control cisplatin.FAPESPCAPESCNPqInstituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo (UNIFESP), 09972-270 Diadema-SP, BrazilDepartamento de Micro, Imuno e Parasitologia, Universidade Federal de São Paulo (UNIFESP), 04023-062 São Paulo-SP, BrazilInstituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo (UNIFESP), 09972-270 Diadema-SP, BrazilDepartamento de Micro, Imuno e Parasitologia, Universidade Federal de São Paulo (UNIFESP), 04023-062 São Paulo-SP, BrazilFAPESP: BIOTA 2011/51739-6FAPESP: 2015/11936-2Web of Scienc

Dammarane Triterpenoids from Carnauba, Copernicia prunifera (Miller) H. E. Moore (Arecaceae), Wax

Phytochemical investigation from carnauba (Copernicia prunifera) wax led to the identification of sixteen dammarane-type triterpenes, including thirteen new characterized as: (24R*)-methyldammara-20,25-dien-3 alpha-ol and a mixture of alkyl (24R*)-methyldammar-25-en- 20-ol-3 beta-carboxylates, together with three previously described triterpenes: carnaubadiol, (24R*)-methyldammara-20,25-dien-3 beta-ol and (24R*)-24-methyldammara-20,25-dien-3-one. Moreover, four fatty alcohols (eicosanol, docosanol, tetracosanol and hexacosanol) as well as four sterols (cholesterol, campesterol, stigmasterol, and sitosterol) were also obtained. These compounds were isolated using classical chromatographic methods and their structures were determined by spectroscopic and chemical methods.Univ Fed Piaui, Dept Quim, BR-64049550 Teresina, PI, BrazilUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 Diadema, SP, BrazilUniv Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210180 Santo Andre, SP, BrazilUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 Diadema, SP, BrazilWeb of Scienc

Evidences of herbal medicine-derived natural products effects in inflammatory lung diseases

Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress (ARDS). Most of these diseases are treated with anti-inflammatory therapy in order to prevent or to reduce the pulmonary inflammation. Herbal medicine-derived natural products have been used in folk medicine and scientific studies to evaluate the value of these compounds have grown in recent years. Many substances derived from plants have the biological effects in vitro and in vivo, such as flavonoids, alkaloids, and terpenoids. Among the biological activities of natural products derived from plants can be pointed out the anti-inflammatory, antiviral, antiplatelet, antitumor anti-allergic activities, and antioxidant. Although many reports have evaluated the effects of these compounds in experimental models, studies evaluating clinical trials are scarce in the literature. This review aims to emphasize the effects of these different natural products in pulmonary diseases in experimental models and in humans and pointing out some possible mechanisms of action.CNPq [300546/2012-2, 304465/2012-7, 476877/2012-1]FAPESP [2010/14831-3, 2011/15817-7, 2008/55359-5]Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Federal University of São Paulo, Diadema-SP 09972-270, BrazilSchool of Medicine, University of São Paulo, São Paulo-SP 01246903, BrazilInstituto de Saúde e Sociedade, Federal University of São Paulo, Santos-SP 11015-020, BrazilInstituto de Ciências Ambientais, Químicas e Farmacêuticas, Federal University of São Paulo, Diadema-SP 09972-270, BrazilInstituto de Saúde e Sociedade, Federal University of São Paulo, Santos-SP 11015-020, BrazilCNPq: 300546/2012-2CNPq: 304465/2012-7CNPq: 476877/2012-1FAPESP: 2010/14831-3FAPESP: 2011/15817-7FAPESP: 2008/55359-5Web of Scienc

Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata

The development of novel drugs for the treatment of leishmaniases continues to be crucial to overcome the severe impacts of these diseases on human and animal health. Several bioactivities have been described in extracts from macroalgae belonging to the Cystoseira genus. However, none of the studies has reported the chemical compounds responsible for the antileishmanial activity observed upon incubation of the parasite with the aforementioned extracts. Thus, this work aimed to isolate and characterize the molecules present in a hexane extract of Cystoseira baccata that was found to be bioactive against Leishmania infantum in a previous screening effort. A bioactivity-guided fractionation of the C. baccata extract was carried out and the inhibitory potential of the isolated compounds was evaluated via the MIT assay against promastigotes and murine macrophages as well as direct counting against intracellular amastigotes. Moreover, the promastigote ultrastructure, DNA fragmentation and changes in the mitochondrial potential were assessed to unravel their mechanism of action. In this process, two antileishmanial meroditerpenoids, (3R)- and (3S)-tetraprenyltoluquinol (1a/1b) and (3R)- and (3S)-tetraprenyltoluquinone (2a/2b), were isolated. Compounds 1 and 2 inhibited the growth of the L. infantum promastigotes (IC50 = 44.9 +/- 4.3 and 94.4 +/- 10.1 mu M, respectively), inducing cytoplasmic vacuolization and the presence of coiled multilamellar structures in mitochondria as well as an intense disruption of the mitochondrial membrane potential. Compound 1 decreased the intracellular infection index (IC50 = 25.0 +/- 4.1 mu M), while compound 2 eliminated 50% of the intracellular amastigotes at a concentration > 88.0 mu M. This work identified compound 2 as a novel metabolite and compound 1 as a biochemical isolated from Cystoseira algae displaying antileishmanial activity. Compound 1 can thus be an interesting scaffold for the development of novel chemotherapeutic molecules for canine and human visceral leishmaniases studies. This work reinforces the evidence of the marine environment as source of novel molecules. (C) 2017 Elsevier Inc. All rights reserved.Portuguese FCT CCMAR/Multi/04326/2013FAPESP [2013/16297-2, 2015/11936-2]CNPq [470853/2012-3]FCT doctoral grants [ SFRH/BD/105541/2014 ]FCT Investigator Programme [IF/00049/2012]info:eu-repo/semantics/publishedVersio

Combined fit to the spectrum and composition data measured by the Pierre Auger Observatory including magnetic horizon effects

The measurements by the Pierre Auger Observatory of the energy spectrum and mass composition of cosmic rays can be interpreted assuming the presence of two extragalactic source populations, one dominating the flux at energies above a few EeV and the other below. To fit the data ignoring magnetic field effects, the high-energy population needs to accelerate a mixture of nuclei with very hard spectra, at odds with the approximate E$^{-2}$ shape expected from diffusive shock acceleration. The presence of turbulent extragalactic magnetic fields in the region between the closest sources and the Earth can significantly modify the observed CR spectrum with respect to that emitted by the sources, reducing the flux of low-rigidity particles that reach the Earth. We here take into account this magnetic horizon effect in the combined fit of the spectrum and shower depth distributions, exploring the possibility that a spectrum for the high-energy population sources with a shape closer to E$^{-2}$ be able to explain the observations

Studies of the mass composition of cosmic rays and proton-proton interaction cross-sections at ultra-high energies with the Pierre Auger Observatory

In this work, we present an estimate of the cosmic-ray mass composition from the distributions of the depth of the shower maximum (Xmax) measured by the fluorescence detector of the Pierre Auger Observatory. We discuss the sensitivity of the mass composition measurements to the uncertainties in the properties of the hadronic interactions, particularly in the predictions of the particle interaction cross-sections. For this purpose, we adjust the fractions of cosmic-ray mass groups to fit the data with Xmax distributions from air shower simulations. We modify the proton-proton cross-sections at ultra-high energies, and the corresponding air shower simulations with rescaled nucleus-air cross-sections are obtained via Glauber theory. We compare the energy-dependent composition of ultra-high-energy cosmic rays obtained for the different extrapolations of the proton-proton cross-sections from low-energy accelerator data

Study of downward Terrestrial Gamma-ray Flashes with the surface detector of the Pierre Auger Observatory

The surface detector (SD) of the Pierre Auger Observatory, consisting of 1660 water-Cherenkov detectors (WCDs), covers 3000 km2 in the Argentinian pampa. Thanks to the high efficiency of WCDs in detecting gamma rays, it represents a unique instrument for studying downward Terrestrial Gamma-ray Flashes (TGFs) over a large area. Peculiar events, likely related to downward TGFs, were detected at the Auger Observatory. Their experimental signature and time evolution are very different from those of a shower produced by an ultrahigh-energy cosmic ray. They happen in coincidence with low thunderclouds and lightning, and their large deposited energy at the ground is compatible with that of a standard downward TGF with the source a few kilometers above the ground. A new trigger algorithm to increase the TGF-like event statistics was installed in the whole array. The study of the performance of the new trigger system during the lightning season is ongoing and will provide a handle to develop improved algorithms to implement in the Auger upgraded electronic boards. The available data sample, even if small, can give important clues about the TGF production models, in particular, the shape of WCD signals. Moreover, the SD allows us to observe more than one point in the TGF beam, providing information on the emission angle