A strategy for the rapid identification of fungal metabolites and the discovery of the antiviral activity of pyrenocine a and harzianopyridon

The isolation and identification of bioactive metabolites from complex extracts obtained from microbial growth media is a time consuming, costly, and labor-intensive task. A strategy to rapidly identify secondary metabolites isolated from extracts obtained from the culture media of marine-derived and endophytic fungal strains is described. Identification was achieved by HPLC-UV-MS and 1H NMR analyses in combination with data obtained from the Dictionary of Natural Products. Among the compounds identified, (-)-naphthoquinoneimine, citreorosein, emodin, pyrenocine A and harzianopyridone displayed moderate to potent antiviral activity. (-)-Naphthoquinoneimine was isolated as the enantiomer of its previously reported dextrorotatory congener, while 6,7-dihydroxy-2,2-dimethyl-4-chromanone is herein reported for the first time as a natural product396720731CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPBEX 4498-14-32010/50190-2; 2013/50228-8; 2011/08064-2; 2008/00331-9; 2013/23153-

Synthesis and antiproliferative activity of novel limonene derivatives with a substituted thiourea moiety

A series of R-(+)-limonene derivatives bearing a substituted thiourea moiety (3-13) and five S-methyl analogs (14-18) were synthesized and evaluated for their in vitro antiproliferative activity against human cancer cell lines. Compounds bearing aromatic substituents (3-6) exhibit cytotastic activity in the full panel of cell lines tested, with GI50 values in the range of 2.5 to 24 µmol L-1. Compounds 3, 10, 12 and 16 were the most active with GI50 values in the range of 0.41 to 3.0 µmol L-1, against different cell lines.No presente trabalho descrevemos a síntese e a avaliação da atividade antiproliferativa, frente a linhagens de células tumorais humanas, de derivados do R-(+)-limoneno (3-18) contendo uma unidade tiouréia substituída. Os derivados com substituintes arílicos (3-6) exibiram atividade citostática frente a todas linhagens testadas, com inibição de 50% do crescimento celular (GI50) em concentrações na faixa de 2,5 a 24 µmol L-1. Os compostos 3, 10, 12 e 16 foram os mais ativos, com GI50 na faixa de 0,41 a 3,0 mmol L-1, frente a diferentes linhagens celulares.954960Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Asymmetric Total Synthesis And Antiproliferative Activity Of Goniothalamin Oxide Isomers.

Goniothalamin oxide (1) is a styryl lactone which was isolated from bark and leaves of several Goniothalamus species. This natural product has some interesting biological properties such as larvicidal and tripanocidal activities. However, no studies on the antiproliferative profile of goniothalamin oxide (1) and its stereoisomers have been reported yet. Here, goniothalamin epoxide (1), isogoniothalamin epoxide (2) and their enantiomers were prepared via epoxidation of (R)-and (S)-goniothalamin (4). A 3:2 molar ratio in favor of goniothalamin oxide (1) and ent-1 was observed from (R)- and (S)-4, respectively, when 3-chloroperbenzoic acid (mCPBA) was employed while an increase to 6:1 molar ratio was achieved with (S,S)-Jacobsen's catalyst. Antiproliferative activity of these epoxides revealed that ent-isogoniothalamin oxide (ent-2) was the most active against the eight cancer cell lines studied. These results indicate that 6S, 7R and 8R absolute configurations are beneficial for the activity of these epoxides.3752-

Sequential extraction of bioactive compounds from melia azedarach L. in fixed bed extractor using CO2, ethanol and water

Melia azedarach L. is a plant with wide use in folk medicine since it contains many bioactive compounds ofinterest. The present study aimed to extract bioactive compounds from M. azedarach fruits by a sequentialprocess in fixed bed using various solvent mixtures. Extractions were performed at 50°C and 300 bar infour sequential steps using supercritical CO2(scCO2), scCO2/ethanol, pure ethanol, and ethanol/watermixture as solvents, respectively. The efficacy of the extraction process was evaluated by extraction yieldand kinetics, and analysis of extracts by: (1) thin layer chromatography (TLC), (2) phenolics content,(3) reduction of surface tension of water, (4) gas chromatography (GCMS), (5) electrospray ionizationmass spectrometry (ESIMS) and (6) antiviral activity. The overall extraction yield reached 45% andTLC analysis showed extracts with different composition. extract obtained from CO2/ethanol mixture(SCEE) exhibited the greatest ability to reduce surface tension of water from 72.4 mN m?1[1] of purewater to 26.9 mN m?1of an aqueous solution of 40 g L?1. The highest phenolics contents were observedin both the hydroalcoholic extract and scCO2/ethanolic extract. Volatile oils were not detected in thesupercritical extracts by GCMS. MS analyses identified the fatty acids: linoleic, palmitic and myristicacid in the supercritical extract (SCE), and the phenolics: caffeic acid and malic acid in the other extracts.In addition, SCE and SCEE extracts showed significant inhibition percentage against Herpes Simplex VirusType 1. The extraction process proposed in the present study produced extracts with significant potentialfor application in food and pharmaceutical industries.Melia azedarach L. is a plant with wide use in folk medicine since it contains many bioactive compounds of interest. The present study aimed to extract bioactive compounds from M. azedarach fruits by a sequential process in fixed bed using various solvent95355363FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2012/20736-9131022/2012-1Bitencourt, R.G., Queiroga, C.L., Montanari Junior, I., Cabral, F.A., Fractionated extraction of saponins from Brazilian ginseng by sequential process using supercritical CO2, ethanol and water (2014) J. Supercritical Fluids, 92, pp. 272-281Al-Rubae, A.Y., The potential uses of Melia azedarach L. As pesticidal and medicinal plant, review (2009) American-Eurasian J. Sustainable Agriculture, 3, pp. 185-194Lorenzi, H., (2003) Árvores Exóticas No Brazil: Madeireiras, Ornamentais e Aromáticas, , Institituto Plantarum de Estudos da Flora Nova Odessa, SPWachsman, M., Martino, V., Gutkind, G.O., Coussio, J.D., Coto, C.E., De Torres, R.A., Antiviral activity of a Melia azedarach plant extract (1982) Fitoterapia, 53, pp. 167-170Andrei, G.M., Lampuri, J.S., Coto, C.E., De Torres, R.A., An antiviral factor from Meliaazedarach L. Prevents Tacaribe virus encephalitis in mice (1986) Experientia, 42, pp. 843-845Wachsman, M.B., Castilla, V., Coto, C.E., Inhibition of foot and mouth disease virus (FMDV) uncoating by a plant-derived peptide isolated from Melia azedarach L. Leaves (1998) Archives of Virology, 143, pp. 581-590Khan, A.V., Ahmed, Q.U., Mir, M.R., Shukla, I., Khan, A.A., Antibacterial efficacy of the seed extracts of Melia azedarach against some hospital isolated human pathogenic bacterial strains (2011) Asian Pacific J. Tropical Biomedicine, 1, pp. 452-455Carpinella, M.C., Miranda, M., Almirón, W.R., Ferrayoli, C.G., Almeida, F.L., Palacios, S.M., In vitro pediculicidal and ovicidal activity of an extract and oil from fruits of Melia azedarach L (2007) J. American Academy of Dermatology, 56, pp. 250-256McKenna, M.M., Abou-Fakhr Hammad, E.M., Farran, M.T., Effect of Melia azedarach (Sapindales: Meliaceae) fruit extracts on Citrus Leafminer Phyllocnistis citrella (Lepidoptera: Gracillariidae) (2013) SpringerPlus, 2, pp. 144-150Scapinello, J., Ribeiros, M.L., Tomazelli, O., Jr., Chiaradia, L.A., Vladimir, J., Oliveira, J.D.M., Effects of supercritical CO2 extracts of Melia azedarach L. on the control of fall armyworm (Spodoptera frugiperda) (2014) J. Supercritical Fluids, 86, pp. 100-107Akihisa, T., Pan, X., Nakamura, Y., Kikuchi, T., Takahashi, N., Matsumoto, M., Ogihara, E., Tokuda, H., Limonoids from the fruits of Melia azedarach and their cytotoxic activities (2013) Phytochemistry, 89, pp. 59-70Yuan, C.M., Zhang, Y., Tang, G.H., Li, Y., He, H.P., Li, S.F., Hou, L., Hao, X.J., Cytotoxic limonoids from Melia azedarach (2013) Planta Medica, 79, pp. 163-168Aoudia, H., Oomah, B.D., Zaidi, F., Zaidi-Yahiaoui, R., Drover, J.C.G., Harrison, J.E., Phenolics, antioxidant and anti-inflammatory activities of Melia azedarach extracts (2013) International J. Applied Research in Natural Products, 6, pp. 19-29Matias, R., Sólon, S., Resende, U.M., Gomes, A., Koller, W.W., Melia azedarach, uso popular x estudos químico e farmacológico: Breve revisão (2002) Ensaios e Ciência, 6, pp. 91-121Yang, Y., Xiao, Y., Liu, B., Fang, X., Yang, W., Xu, J., Comparison of headspace solid-phase microextraction with conventional extraction for the analysis of the volatile components in Melia azedarach (2011) Talanta, 86, pp. 356-361Aoudia, H., Ntalli, N., Aissani, N., Yahiaoui-Zaidi, R., Caboni, P., Nematotoxic phenolic compounds from Melia azedarach against Meloidogyne incognita (2012) J. Agricultural and Food Chemistry, 60, pp. 11675-11680Orhan, I.E., Guner, E., Ozturk, N., Senol, F.S., Erdem, S.A., Kartal, M., Sener, B., Enzyme inhibitory and antioxidant activity of Melia azedarach L. Naturalized in Anatolia and its phenolic acid and fatty acid composition (2012) Industrial Crops and Products, 37, pp. 213-218Chiffelle, I.G., Huerta, A.F., Lizana, D.R., Physical and chemical characterization of Melia azedarach L. Fruit and leaf for use as botanical insecticide (2009) Chilean J. Agricultural Research, 69, pp. 38-45Seffrin, R.C.A.S., Corrêa Costa, E., Borges, L., Corralo Borges, V., Do Nascimento, P.C., Bastos Dequech, S.T., Sausen, C.D., Extratos aquosos de frutos verdes de Melia azedarach L. Var. Azedarach: Investigação da presença de cianeto e avaliação toxicológica (2011) Biotemas, 21, pp. 143-147Brunner, G., Supercritical fluids: Technology and application to food processing (2005) J. Food Engineering, 67, pp. 21-33Seabra, I.J., Braga, M.E.M., Batista, M.T., De Sousa, H.C., Effect of solvent (CO2/ethanol/H2O) on the fractionated enhanced solvent extraction of anthocyanins from elderberry pomace (2010) J. Supercritical Fluids, 54, pp. 145-152Paula, J.T., Paviani, L.C., Foglio, M.A., Sousa, I.M.O., Cabral, F.A., Extraction of anthocyanins from Arrabidaea chica in fixed bed using CO2 and CO2/ethanol/water mixtures as solvents (2013) J. Supercritical Fluids, 81, pp. 33-41Garmus, T.T., Paviani, L.C., Queiroga, C.L., Magalhães, P.M., Cabral, F.A., Extraction of phenolic compounds from pitanga (Eugenia uniflora L.) leaves by sequential extraction in fixed bed extractor using supercritical CO2, ethanol and water as solvents (2014) J. Supercritical Fluids, 86, pp. 4-14Paula, J.T., Paviani, L.C., Foglio, M.A., Sousa, I.M., Duarte, G.H., Jorge, M.P., Eberlin, M.N., Cabral, F.A., Extraction of anthocyanins and luteolin from Arrabidaea chica by sequential extraction in fixed bed using supercritical CO2, ethanol and water as solvents (2014) J. 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Antiproliferative Effect of Benzophenones and their Influence on Cathepsin Activity

The antiproliferative activity of two prenylated benzophenones isolated from Rheedia brasiliensis. the tri-prenylated garciniaphenone and the tetraprenylated benzophenone 7-epiclusianone, was investigated against human cancer cell lines. The antiproliferative activity on melanoma (UACC-62), breast (MCF-7), drug-resistant breast (NCI-ADR), lung/non-small cells (NCI460), ovarian (OVCAR 03), prostate (PC03), kidney (786-0), lung (NCI-460) and tongue (CRL-1624 and CRL-1623) cancer cells was determined using spectrophotometric quantification of the cellular protein content. The effect of these benzophenones on the activity of cathepsins B and G was also investigated. Garciniaphenone displayed cytostatic activity in all cell lines, whereas 7-epiclusianone showed a dose-dependent cytotoxic effect. The IC(50) values for cell proliferation revealed that 7-epiclusianone is more active than garciniaphenone against most of the cell lines. Furthermore, the antiproliferative effects demonstrated by garciniaphenone and 7-epiclusianone were related to their cathepsin inhibiting properties. In conclusion, 7-epiclusianone is a promising naturally occurring agent which displays multiple inhibitory effects which may be working in concert to inhibit cancer cell proliferation in vitro. The putative pathway by which 7-epiclusianone affects cancer cell development may involve cathepsin inhibition. Copyright (C) 2009 John Wiley & Sons, Ltd.CNPq[141253/2005-3]UNICAMP/FAEP[1612/04 75/2

Antiproliferative effect of benzophenones and their infl uence on cathepsin activity.

The antiproliferative activity of two prenylated benzophenones isolated from Rheedia brasiliensis, the triprenylated garciniaphenone and the tetraprenylated benzophenone 7-epiclusianone, was investigated against human cancer cell lines. The antiproliferative activity on melanoma (UACC-62), breast (MCF-7), drug-resistant breast (NCI-ADR), lung/non-small cells (NCI460), ovarian (OVCAR 03), prostate (PC03), kidney (786-0), lung (NCI-460) and tongue (CRL-1624 and CRL-1623) cancer cells was determined using spectrophotometric quantifi cation of the cellular protein content. The effect of these benzophenones on the activity of cathepsins B and G was also investigated. Garciniaphenone displayed cytostatic activity in all cell lines, whereas 7- epiclusianone showed a dose-dependent cytotoxic effect. The IC50 values for cell proliferation revealed that 7-epiclusianone is more active than garciniaphenone against most of the cell lines. Furthermore, the antiproliferative effects demonstrated by garciniaphenone and 7-epiclusianone were related to their cathepsin inhibiting properties. In conclusion, 7-epiclusianone is a promising naturally occurring agent which displays multiple inhibitory effects which may be working in concert to inhibit cancer cell proliferation in vitro. The putative pathway by which 7-epiclusianone affects cancer cell development may involve cathepsin inhibition

Antiproliferative effect of benzophenones and their influence on cathepsin activity

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP – FINANCIADORA DE ESTUDOS E PROJETOSThe antiproliferative activity of two prenylated benzophenones isolated from Rheedia brasiliensis, the triprenylated garciniaphenone and the tetraprenylated benzophenone 7-epiclusianone, was investigated against human cancer cell lines. The antiproliferative activity on melanoma (UACC-62), breast (MCF-7), drug-resistant breast (NCI-ADR), lung/non-small cells (NCI460), ovarian (OVCAR 03), prostate (PC03), kidney (786-0), lung (NCI-460) and tongue (CRL-1624 and CRL-1623) cancer cells was determined using spectrophotometric quantification of the cellular protein content. The effect of these benzophenones on the activity of cathepsins B and G was also investigated. Garciniaphenone displayed cytostatic activity in all cell lines, whereas 7-epiclusianone showed a dose-dependent cytotoxic effect. The IC(50) values for cell proliferation revealed that 7-epiclusianone is more active than garciniaphenone against most of the cell lines. Furthermore, the antiproliferative effects demonstrated by garciniaphenone and 7-epiclusianone were related to their cathepsin inhibiting properties. In conclusion, 7-epiclusianone is a promising naturally occurring agent which displays multiple inhibitory effects which may be working in concert to inhibit cancer cell proliferation in vitro. The putative pathway by which 7-epiclusianone affects cancer cell development may involve cathepsin inhibition.The antiproliferative activity of two prenylated benzophenones isolated from Rheedia brasiliensis, the triprenylated garciniaphenone and the tetraprenylated benzophenone 7‐epiclusianone, was investigated against human cancer cell lines. The antiproliferative activity on melanoma (UACC‐62), breast (MCF‐7), drug‐resistant breast (NCI‐ADR), lung/non‐small cells (NCI460), ovarian (OVCAR 03), prostate (PC03), kidney (786‐0), lung (NCI‐460) and tongue (CRL‐1624 and CRL‐1623) cancer cells was determined using spectrophotometric quantification of the cellular protein content. The effect of these benzophenones on the activity of cathepsins B and G was also investigated. Garciniaphenone displayed cytostatic activity in all cell lines, whereas 7‐epiclusianone showed a dose‐dependent cytotoxic effect. The IC50 values for cell proliferation revealed that 7‐epiclusianone is more active than garciniaphenone against most of the cell lines. Furthermore, the antiproliferative effects demonstrated by garciniaphenone and 7‐epiclusianone were related to their cathepsin inhibiting properties. In conclusion, 7‐epiclusianone is a promising naturally occurring agent which displays multiple inhibitory effects which may be working in concert to inhibit cancer cell proliferation in vitro. The putative pathway by which 7‐epiclusianone affects cancer cell development may involve cathepsin inhibition243379383CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP – FINANCIADORA DE ESTUDOS E PROJETOSCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP – FINANCIADORA DE ESTUDOS E PROJETOS141253/2005-31110/0