Dissertations / Theses on the topic 'Natural products and bioactive compounds'
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Heltzel, Carl E. "Structural and synthetic studies of bioactive natural products." Diss., Virginia Tech, 1993. http://hdl.handle.net/10919/40067.
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Bioassay directed fractionation of the methyl ethyl ketone extract of Crescentia cujete resulted in the isolation of nine bioactive compounds, and detailed spectroscopic interpretation led to the assignment of their structures as (2S,3S)-3-hydroxy-5,6-dimethoxy dehydroiso-α-Iapachone [2.10], (2R)-5,6- dimethoxydehydroiso-α-Iapachone [2.11], (2R)-5-methoxy dehydroiso-alapachone [2.12], 5-hydroxy-2-(1'-hydroxyethyl)naphtho[2,3-b ]furan-4,9-dione [2.13], 2-(1 '-hydroxyethyl)naphtho[2,3-b ]furan-4,9-dione [2.14]' 2-isopropenylnaphtho[ 2,3-b ]furan-4,9-dione [2.15], 5-hydroxydehydro-iso-a-Iapachone [2.16], 3-hydroxymethylfuro[3,2-b ]naphtho[2,3-d]furan-5,10-dione [2.17], and 9- hydroxy-3-hydroxymethylfuro[3,2-b ]naphtho[2,3-d]furan-5,10-dione [2.18]. Compounds 2.10-2.12 are new, showing selective activity towards DNA repair-deficient yeast mutants. The selective DNA damaging activity of known compounds 2.13-2.16 is reported herein for the first time. Compounds 2.17 and 2.18 also show DNA damaging activity, and possess a novel fused ring system.
The bioactive sterols ergosta-5-24(28)-diene-3β,7α-diol [3.1] and 24,28- epoxyergost-5-ene-3β,7α-diol [3.2], originally isolated from Pseudobersama mossambicensis, have been synthesized from stigmasterol. In addition to these sterols, some of their analogs were prepared, and the bioactivity of all compounds were assessed.Ph. D.
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Dowle, Katie Orlagh. "New nitrogenous spongian diterpenes from the New Zealand marine sponge Darwinella oxeata : a thesis submitted to the Victoria University of Wellington in fulfilment of the requirements for the degree of Master of [Science] in Chemistry /." ResearchArchive@Victoria e-Thesis, 2008. http://hdl.handle.net/10063/626.
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Eaton, Alexander Lee. "Isolation and Synthesis of Bioactive Compounds from Plants." Diss., Virginia Tech, 2015. http://hdl.handle.net/10919/64367.
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As a part of a continuing search for bioactive compounds with the International Cooperative Biodiversity Group (ICBG), and in collaboration with the Natural Products Discovery Institute of the Institute for Hepatitis and Virus Research (IHVR), twelve plant extracts were investigated for their antiproliferative activity against the A2780 cell line, three plant extracts were investigated for their antimalarial activity against Plasmodium falciparum, and three plant extracts were investigated for their anti-inflammatory activity (PPAR-y inhibition). Bioassay-guided fractionation of extracts led to the identification of four new antiproliferative compounds (2.1-2.3, 3.1), five new anti-inflammatory compounds (6.4a, 6.5a-b, 6.6a, 6.6c), and twenty-eight known compounds from eight of the extracts. In addition, mallotojaponin C, an antimalarial natural product, and derivatives were synthesized and investigated for their antimalarial activity.Ph. D.
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Thwala, Sazi Selby. "Investigation of the natural products composition from the seaweed ulva capensis." University of Western Cape, 2019. http://hdl.handle.net/11394/7888.
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>Magister Scientiae - MScIn modern society, diversity of marine macroalgae has become an inspiration for pharmaceutical companies and researchers because of their numerous health benefits, and a great deal of interest has developed towards the isolation of bioactive compounds to identify novel marine natural products that could eventually be developed into therapeutics or pharmaceutical products. Furthermore, marine macroalgae are valuable source of structurally diverse metabolites with scientifically proven reports. The search continues as there are many natural bioactive compounds that are in the womb of the ocean which are still a mystery. Thus, the present study investigates the natural products from green seaweed Ulva capensis.
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Akintunde, Olaitan G. "Production of an Antibiotic-like Activity by Streptomyces sp. COUK1 under Different Growth Conditions." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etd/2412.
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Streptomyces are known to produce a large variety of antibiotics and other bioactive compounds with remarkable industrial importance. Streptomyces sp. COUK1 was found as a contaminant on a plate in which Rhodococcus erythropolis was used as a test strain in a disk diffusion assay and produced a zone of inhibition against the cultured R. erythropolis. The identity of the contaminant was confirmed as Streptomyces through 16S rRNA sequencing. This Streptomyces produces a strong inhibitory compound in different growth media. A culture extract from inorganic salts starch agar was found to be very active; producing a large zone of inhibition against several Gram positive and Gram negative test strains. The active molecules in this extract have been detected via TLC and bioautography. The difference in the antibacterial activity and chromatographic properties of extracts recovered from different growth media suggests that this Streptomyces strain could produce more than one type of inhibitory compound.
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PAN, CHENGQIAN. "Discovery of Novel Bioactive Compounds from a Rare Actinomycete Amycolatopsis sp. 26-4." Kyoto University, 2020. http://hdl.handle.net/2433/259019.
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Chamyuang, Sunita. "Application of selective methods in the search for new bioactive natural products from fungi." Thesis, University of Canterbury. School of biological Science, 2010. http://hdl.handle.net/10092/3702.
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The work undertaken explored the potential for discovery of new bioactive metabolites from soil fungi. The research developed selective mycological isolation techniques and maximised metabolite production from active selected fungi by application of the OSMAC approach and concept of hormesis. Novel active compounds were discovered and many other known compounds characterised.
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Inuki, Shinsuke. "Total Synthesis of Bioactive Natural Products by Palladium-Catalyzed Domino Cyclization of Allenes and Related Compounds." 京都大学 (Kyoto University), 2011. http://hdl.handle.net/2433/142485.
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El, Marrouni El Ghazaoui Abdellatif. "Synthesis of unusual alpha-amino acids and study of the effect of their incorporation into antimicrobial peptides. Total synthesis of biactive marine natural products and analogues thereof." Doctoral thesis, Universitat de Girona, 2012. http://hdl.handle.net/10803/80815.
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The principle theme of this thesis was the synthesis of bioactive compounds. To this end, this work was focus on two main projects. The first one, which was carried out in the Department of Chemistry of the University of Girona under the supervision of Dr Montserrat Heras, concerned the synthesis of new unnatural amino acids bearing a pyrimidine ring within their side chain for incorporation into the antimicrobial peptide BP100 following a rational design in order to improve its biological profile. On the other hand, the second chapter of this thesis was developed in collaboration with the Laboratoire de Chimie Organique (ESPCI-ParisTech, Paris, France) under the guidance of Pr Janine Cossy and Dr Arseniyadis. This chapter was centered on the total synthesis of three marine natural products with complex structures and interesting biological activities: acremolide B, (–) bitungolide F and lyngbouilloside.Aquesta tesi s'ha centrat en la preparació de nous compostos bioactius seguint dues estratègies diferents. El primer projecte es va portar a terme sota la supervisió de la Dra. Montserrat Heras del grup LIPPSO del Departament de Química i ha permés el desenvolupament de noves metodologies per la síntesi de nous aminoàcids no naturals. i el seu ús en la preparació d'anàlegs del pèptid antimicrobià BP100 amb l'objectiu de millorar-ne les propietats biològiques. El segon projecte és fruit de la col•laboració amb la Prof. Janine Cossy i el Dr. Stellios Arseniyadis del "Laboratoire de Chimie Organique" de l'Ecole Superieur de Physique et Chimie Industrielles (ESPCI-ParisTech, Paris, França). I ha permés posar a punt tres estratègies sintètiques convergents i versàtils per l’obtenció de tres productes naturals de gran complexitat estructural i interessants activitats biològiques – l'acremolide B, la bitungolide F i la lyngbouilloside – aïllats recentment del fons marí de diferents punts del món.
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Elias, Luciana Mecatti. "Bioprospecção de fungos endofíticos isolados de guaranazeiros da Amazônia." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/11/11138/tde-05012016-111344/.
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Fungos do gênero Colletotrichum são considerados um dos principais fitopatógenos do mundo, comprometendo diversas culturas e causando danos econômicos e sociais para diversos países, inclusive o Brasil. Apesar de medidas de controle já serem empregadas, estas nem sempre são eficazes, motivo pelo qual se faz necessária a busca por novas opções de controle que possam atuar no manejo integrado. Dentre estas, encontram-se os metabólitos secundários produzidos por fungos endofíticos, os quais estão envolvidos na produção de compostos de interesse biotecnológico, com aplicações em diversas áreas, inclusive a agronômica. Neste contexto, o presente trabalho de doutorado teve por objetivo explorar o potencial biológico e químico de metabólitos secundários produzidos por fungos endofíticos isolados de guaranazeiros da Amazônia, avaliando sua atividade antifúngica \"in vitro\" a Colletotrichum gloeosporioides, isolado da cultura do guaranazeiro, a C. acutatum e C. gloeosporioides, isolados da cultura do pimentão. Para tanto, 16 linhagens de fungos endofíticos foram avaliadas em ensaio biológico por cultivo pareado e pelo método de difusão em disco contra Colletotrichum spp. Observou-se que quatro linhagens se mostraram mais promissoras, as quais foram selecionadas para o estudo de bioprospecção. A partir do extrato bruto do endófito Aspergillus flavus (272) foi isolado o composto ativo asperfuran, que apresentou atividade inibitória aos três fitopatógenos, com CI50 < 100 μg disco-1, semelhante ao fungicida comercial difenoconazol. A partir do extrato bruto de Xylaria sp. (214) foi isolado o composto ativo citocalasina D, que apresentou atividade inibitória a C. gloeosporioides isolado do guaranazeiro, com CI50 > 500 μg disco-1. A partir do extrato bruto de Xylaria sp. (249) foi isolado o composto ativo ácido pilifórmico, que apresentou atividade inibitória a C. gloeosporioides isolado do guaranazeiro, com CI50 de 500 μg disco-1 e à C. acutatum isolado o pimentão, com CI50 de 300 μg disco-1. E, a partir do extrato bruto de Talaromyces aculeatus (507) foram isolados três compostos, da classe dos ésteres ftalicos, sendo um ativo. A fração antecessora destes três compostos apresentou atividade inibitória a C. gloeosporioides isolado do guaranazeiro, com CI50 > 500 μg disco-1. A partir do extrato bruto de T. aculeatus também foi isolado um composto ativo parcialmente identificado e um composto ativo semi-purificado. A fração antecessora destes dois compostos apresentou atividade inibitória aos dois C. gloeosporioides, com CI50 > 300 μg disco-1 e a C. acutatum, com CI50 em torno de 150 μg disco-1. A atividade antifúngica destes compostos a fungos do gênero Colletotrichum está sendo relatada pela primeira vez neste estudo.Colletotrichum fungi are considered one of the main pathogens in the world, affecting different cultures and causing social and economic damage to several countries, including Brazil. Despite control measures already being employed, these are not always effective, which is why the search for new control options that can act in the integrated management is necessary. Among these, the secondary metabolites produced by endophytes are involved in the production of compounds of biotechnological interest, with applications in several areas, including the agronomic. In this context, this study aimed to explore the biological and chemical potential of secondary metabolites produced by endophytic fungi isolated from the Amazonian guarana, evaluating their antifungal activity \"in vitro\" to Colletotrichum gloeosporioides, isolated from the culture of guarana and C. acutatum and C. gloeosporioides, isolated from the red pepper crop. For this purpose, 16 strains of endophytic fungi were evaluated in biological assay of dual culture and disk diffusion method against Colletotrichum spp. Four strains of these strains presented promising results which were selected for bioprospecting. From the crude extract of the endophyte Aspergillus flavus (272) was isolated the active compound asperfuran, which showed inhibitory activity to three pathogens, with IC50 <100 μg disk-1, similar to the commercial fungicide difenoconazole. From the crude extract of Xylaria sp. (214) was isolated the active compound cytochalasin D, which showed inhibitory activity against C. gloeosporioides isolated from guarana (IC50> 500 μg disk-1). From the crude extract of Xylaria sp. (249) was isolated the active compound piliformic acid, which showed inhibitory activity against C. gloeosporioides isolated from guarana (IC50 of 500 μg disk-1) and C. acutatum isolated from red pepper (IC50 of 300 μg disk-1). And from the crude extract of Talaromyces aculeatus (507) were isolated three compounds, of phthalate esters class, one of them with activity. The predecessor fraction of these three compounds showed inhibitory activity against C. gloeosporioides isolated from guarana (IC50> 500 μg disk-1). From the crude extract of T. aculeatus it was also isolated a partially identified active compound and a semi-purified active compound. The predecessor fraction of these two compounds showed inhibitory activity to both C. gloeosporioides (IC50> 300 μg disk-1) and to C. acutatum (IC50 around 150 μg disk-1). The antifungal activity of the compounds isolated in this study is being reported for the first time against fungus of the genus Colletotrichum.
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Salinas-Roca, Blanca. "Preserving natural attributes of mango products by non-thermal technologies." Doctoral thesis, Universitat de Lleida, 2017. http://hdl.handle.net/10803/405840.
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Els consumidors demanden nous productes a base de fruites -com els a punt per menjar-, segurs,
saludables i amb propietats similars als naturals. L’objecte d’estudi d’aquesta tesi doctoral fou
avaluar l’impacte de tractaments no tèrmics en propietats de qualitat de diversos productes de
mango: tallat, suc i puré.
Per una banda, l’efecte de diferents recobriments a base de polisacàrids, alginat (AL), quitosan
(CH), pectina (PE) i carboximetilcel·lulosa (CMC), es va avaluar en la conservació de la qualitat
del mango tallat. També, l’efecte dels polsos de llum (PL) combinats amb el recobriment AL i la
immersió en àcid màlic (MA) va permetre allargar la conservació dels atributs naturals durant 14
dies. D’altra banda, es va estudiar la influència dels polsos elèctrics d’alta intensitat de camp
HIPEF a 35 kV/cm, 4 μs- pols bipolar, 200 Hz i 50- 2000 μs en la reducció de població de
Listeria innòcua, l’activitat enzimàtica, les propietats sensorials així com el contingut de
bioactius. En aquest sentit el contingut de fenols en el suc tractat per HIPEF (1800 μs) va millorar
després de 59 dies. Finalment, es va estudiar l’impacte del tractament d’alta pressió hidrostàtica
(HHP) (400, 450, 500 MPa durant 0 a 16 min a 34 o 59°C) en les propietats fisicoquímiques i
enzimàtiques, com també en el contingut de compostos bioactius del puré de mango.
Aquesta investigació mostra la viabilitat de la conservació dels derivats de fruita mitjançant
tecnologies no tèrmiques.Consumers are currently demanding safe, healthy and novel fruit products, such as ready-to-eat, with natural attributes. Therefore, the aim of the present doctoral thesis was to assess the impact of non-thermal treatments on quality properties of various mango products: fresh-cut, juice and puree. On one hand, the effect of different polysaccharide-based coatings, alginate (AL), chitosan (CH), pectin (PE) and carboxymethylcellulose (CMC) was evaluated on the quality preservation of fresh-cut mango. Also in fresh-cut mango, the effect of pulsed light (PL) combined with AL coating and malic acid (MA) dipping extended preservation of natural attributes throughout 14 days. On the other hand, the influence of high intensity pulsed electric fields (HIPEF) at 35 kV/cm, 4 μs- bipolar pulses, 200 Hz and 50-2000 μs in mango juice was studied in the reduction of Listeria innocua population, enzymatic activities, physicochemical and sensorial attributes as well as the content of bioactive compounds. In this sense, phenolic content in mango juice treated with HIPEF (1800 μs) was improved after 59 days. Finally, the impact of high hydrostatic pressure (HHP) treatments (400, 450, 500 MPa for 0 to 16 min at 34 or 59°C) on physicochemical, enzymatic properties and bioactive compounds of mango puree was observed. This research reveals the feasibility of preserving fruit products by non-thermal technologies.
Los consumidores piden nuevos productos a base de frutas, como los listos para el consumo, seguros, saludables y con propiedades similares a los naturales. Por lo tanto, el objeto de estudio de la presente tesis doctoral fue evaluar el impacto de tratamientos no térmicos en la calidad de diversos productos de mango: cortado, zumo y puré. Por un lado, el efecto de diferentes recubrimientos a base de polisacáridos, alginato (AL), quitosano (CH), pectina (PE) y carboximetilcelulosa (CMC) se evaluó en la conservación de la calidad del mango cortado. También, el efecto de los pulsos de luz (PL) combinado con el recubrimiento AL y la inmersión en ácido málico (MA) permitió alargar la conservación de los atributos naturales durante 14 días. Por otro lado, se estudió en el zumo de mango la influencia de los pulsos eléctricos de alta intensidad de campo (HIPEF) a 35 kV/cm, 4 μs- pulso bipolar, 200 Hz y 50- 2000 μs en la reducción de población de Listeria innocua, la actividad enzimática, las propiedades sensoriales así como el contenido de bioactivos. En este sentido el contenido de fenoles en el zumo de mango tratado por HIPEF (1800 μs) mejoró después de 59 días. Finalmente, el impacto del tratamiento por alta presión hidrostática (HHP) (400, 450, 500 MPa de 0 a 16 min a 34 o 59°C) se observó en las propiedades fisicoquímicas y enzimáticas y en el contenido de compuestos bioactivos en el puré de mango. La presente investigación muestra la viabilidad de la conservación de derivados de frutas mediante tecnologías no térmicas.
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Pereira, Daiane. "Desenvolvimento de microcápsulas bioativas de coprodutos de suco e vinho da uva visando sua aplicação como antioxidante natural em patê de carne de frango." Universidade Tecnológica Federal do Paraná, 2015. http://repositorio.utfpr.edu.br/jspui/handle/1/1505.
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CAPESO objetivo do trabalho foi avaliar a capacidade antioxidante de extratos hidroalcoólicos e microencapsulados, por spray dryer, de coprodutos do vinho e suco da uva das variedades Bordô e Niágara (Vitis labrusca) e aplicar em patê cremoso de carne de frango para avaliar a inibição da oxidação lipídica e a aceitação sensorial do produto. Os coprodutos da uva foram extraídos individualmente com etanol 80% em shaker, a 40 ºC/60 minutos, concentrado em evaporador rotativo e microencapsulado em spray dryer com maltodextrina 10 DE e amido modificado (Capsul®). As amostras pulverizadas em spray dryer sofreram influência do agente encapsulante utilizado, e as amostras microencapsuladas com maltodextrina 10 DE obtiveram maior eficiência. A microencapsulação dos coprodutos originou microesferas lisas, rugosas, homogêneas quanto à forma e estrutura e sem fissuras ou rachaduras. A análise de infravermelho com transformada de Fourrier (IVTF) mostrou que os compostos bioativos permaneceram nos extatos mesmo depois da microencapsulação. Os extratos hidroalcoólicos e microencapsulados apresentaram alta atividade antioxidante in vitro, sendo esta atividade atribuída à presença de compostos fenólicos totais, antocianinas e flavonoides totais. Pela técnica de Cromatografia Líquida de Alta Eficiência (CLAE) foi possível identificar e quantificar seis compostos fenólicos (ácido gálico, cafeico, cumárico, ferrúlico, vanílico e trans-resveratrol). O extrato do coproduto da uva bordô vinho, safra 2014 microencapsulado com maltodextrina (CUBV2M (MD)) e o extrato hidroalcoólico liofilizado coproduto uva bordô vinho, safra 2014 (CUBV2) foram escolhidos para aplicação em patê cremoso de frango por apresentar maior teor de compostos fenólicos com elevada atividade antioxidante. A formulação base do patê cremoso de frango foi elaborada com carne de frango, pele de frango e condimentos e foi dividida em quatro tratamentos: o primeiro foi designado como controle e nenhum ingrediente adicional foi incluído (T1). O segundo lote foi prepardo adicionando eritorbato de sódio (T2). O terceiro lote recebeu o extrato etanólico liofilizado CUBV2 (T3). O quarto lote recebeu o extrato microencapsulado CUBV2M (MD) (T4). A estabilidade oxidativa dos patês foi avaliada pelo teor de substâncias reativas ao ácido tiobarbitúrico (TBARS) e pela coloração no dia do processamento e semanalmente por 41 dias. Pela diferença total de cor (ΔE), em relação ao controle (T1), apenas o T4 apresentou influência visualmente perceptível, durante o período de estocagem. Os patês adicionados de 0,3% de CUBV2 e CUBV2M (MD) demonstraram resultados satisfatórios pela análise de TBARS e estavam microbiologicamente de acordo com à legislação vigente. Os índices de aceitabilidade para a avaliação global foram superiores a 70% para T1, T2 e T3 podendo estes extratos de coprodutos de vinho de uva ser considerados uma alternativa aos antioxidantes sintéticos em patês cremosos.
The objective of this study was to evaluate the antioxidant activity of hydroalcoholic extracts and microencapsulated by spray dryer, of different samples of co-products of wine and juice grape varieties Bordô and Niagara (Vitis labrusca) and apply creamy pate of chicken to verify the inhibition lipid oxidation and the acceptance of this product. The grape co-products were extracted individually with ethanol (80%) in shaker at 40 °C / 60 min, concentrated and microencapsulated in spray dryer with maltodextrin 10 DE and capsul®. The dried samples spray dryer were influenced by the encapsulating agent used, where the microencapsulated samples with maltodextrin obtained better efficiency. Microencapsulation of co-products originated smooth beads and other rough, homogeneous in form and structure, without fissures or cracks. The Infrared Fourier Transform analysis (FTIR) showed that the microencapsulated bioactive compounds in the extracts remained even after subjected to drying by spray drying. The hydroalcoholic and microencapsulated extracts showed high phenolic compounds, anthocyanins and flavonoids with antioxidant activity. For the HPLC technique it was possible to identify and quantify six patterns of phenolic compounds (gallic acid, caffeic, coumaric, ferulic, vanillic and trans-resveratrol). The CBGW2 and CBGW2M (MD) extracts were chosen to be applied in creamy pate due to the best levels of phenolic compounds with antioxidant activity. The basic formulation of creamy chicken pate was made with chicken meat, chicken skin and spices and was divided into four treatments: The first was designated as the control and no additional ingredients were included (T1). The second lot was designated as a positive control and was prepared by adding sodium eritorbate (T2). The third lot received liophilized extract CBGW2 (T3). The fourth lot received the CBGW2M (MD) extracts. The stability of chicken meat pates was performed on the day of processing and weekly at 41 days in 4º C by thiobarbituric acid reactive substances index (TBARS) and color. By (ΔE) in color analyses, compared to the control (T1), only the T4 presented visually perceptible influence during the storage period. The pates added 0.3% CBGW2 and CBGW2M (MD) showed satisfactory results for TBARS analysis and were microbiologically according to law. Acceptability levels for the overall evaluation were greater than 70% for T1, T2 and T3 and these extracts of grape wine co-products can be considered an alternative to synthetic antioxidants in pates creamy.
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Manirujjaman. "Identification of bioactive compounds in native plants and their effects on wound healing." Thesis, Queensland University of Technology, 2019. https://eprints.qut.edu.au/132475/1/Manirujjaman_Manirujjaman_Thesis.pdf.
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This project has made an important contribution towards understanding the medicinal potential of three Australian plants. The identification of novel and previously isolated wound healing compounds from the methanolic extracts of the target plants demonstrate that Australian natives are a rich source of bioactive constituents, which may have a therapeutic role for the future treatment of chronic non-healing wounds.
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Reis, Gislâine Vicente dos. "Isolamento bioguiado de compostos de actinobactérias com atividade fungitóxica." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/11/11138/tde-26102017-172809/.
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As espécies patogênicas do gênero Colletotrichum apresentam importância mundial, pois causam danos a várias culturas de interesse agronômico. Diversas medidas de controle são empregadas, mas estas nem sempre são eficazes devido à ocorrência de linhagens resistentes. Desta forma, se faz necessário a busca por novos compostos que possam ser utilizados no manejo integrado desta doença. Os produtos naturais isolados de micro-organismos podem ser uma alternativa para o desenvolvimento de novos defensivos agrícolas. Dentre os micro-organismos, as actinobactérias são conhecidas pela produção de inúmeros compostos antimicrobianos. Neste contexto, o presente estudo teve como objetivo o isolamento e a identificação de compostos antifúngicos produzidos por actinobactérias da rizosfera de guaranazeiros. Para isto, a seleção de actinobactérias foi baseada em dois ensaios. No primeiro, as 65 actinobactérias foram avaliadas em ensaio de cultivo pareado frente ao fitopatógeno Colletotrichum gloeosporioides. Destas, os isolados mais promissores foram AM1 (43,78 % de inibição do crescimento micelial), AM3 (43,98 %), AM18 (37,86 %), AM25 (43,17 %), AM30 (47,12 %), AM61 (40,12 %) e AM68 (47,94 %). No segundo ensaio, estes isolados foram cultivados em meio BD e, após o cultivo, o meio metabólico foi submetido a três métodos de extração: (a) partição líquido-líquido com n-butanol; (b) partição líquido-líquido com acetato de etila e (c) coluna sílica gel C18. As frações obtidas a partir das três metodologias foram avaliadas pelo método de difusão em disco de papel contra C. gloeosporioides. Neste ensaio de difusão em disco foram selecionadas as linhagens AM1(n-butanol), AM3 (acetato de etila) e AM25 (C18) para o estudo de bioprospecção. Estas foram identificadas por técnicas moleculares como pertencentes ao gênero Streptomyces. A partir do extrato bruto da Streptomyces sp. AM1 foi isolado um composto análogo do ácido proclavamínico, o qual apresentou atividade mínima inibitória (MIC) de 1,25 mg mL-1 contra o fitopatógeno C. gloeosporioides. Da linhagem Streptomyces sp. AM3 foi isolado o composto streptimidona que apresentou MIC de 1,25 mg mL-1. Já no estudo de Streptomyces sp. AM25 um composto não identificado apresentou MIC de 2,50 mg mL-1. Estes três compostos apresentaram atividade superior aos fungicidas Captan SC® (Captana) e Dithane NT® (Mancozeb), e inferior ao Score® (Difenoconazol). A atividade antifúngica destes compostos ao C. gloeosporioides está sendo relatada pela primeira vez.The pathogenic species of the genus Colletotrichum present importance worldwide because they cause damage to numerous crops of agronomic interest. Several control methods are employed, but they are not always effective due to the occurrence of resistant strains. Thus, it is necessary searching for new compounds that can be used in the integrated management of this disease. Natural products isolated from microorganisms can be an alternative for the development of new agricultural pesticides. Among microorganisms, actinobacteria are known to produce numerous antimicrobial compounds. In this context, the present study aimed to isolate and identify antifungal compounds produced by actinobacteria from guarana rhizosphere. For this, the selection of actinobacteria was based on two tests. In the first one, the 65 actinobacteria were evaluated in paired cultivation test against the plant pathogen Colletotrichum gloeosporioides. Among them, the most promising isolates were AM1 (43.78% inhibition), AM3 (43.98%), AM18 (37.86%), AM25 (43.17%), AM30 (47.12%), AM61 (40.12%) and AM68 (47.94%). In the second assay, these isolates were cultured in BD medium and, after culturing, the metabolic medium was subjected to three extraction methods: (a) liquid-liquid partition with n-butanol; (B) liquid-liquid partition with ethyl acetate and (c) silica gel column C18. The fractions obtained from the three methodologies were evaluated by paper disc diffusion method against C. gloeosporioides. In this disk diffusion assay, the strains AM1 (n-butanol), AM3 (ethyl acetate) and AM25 (C18) were selected for the bioprospecting study. These were identified by molecular techniques as belonging to the genus Streptomyces. From the crude extract of Streptomyces sp. AM1 the analogous compound proclavaminic acid was isolated, which presented minimal inhibitory activity (MIC) of 1.25 mg mL -1 against the plant pathogen C. gloeosporioides. From Streptomyces sp. AM3, the compound streptimidone was isolated, which presented MIC of 1.25 mg mL-1. In the study of Streptomyces sp. AM25 an unidentified compound had MIC of 2.50 mg mL-1. These three compounds presented superior activity to the fungicides Captan SC® (Captan) and Dithane NT® (Mancozeb), and inferior to the Score® (Difenoconazole). The antifungal activity of these compounds to C. gloeosporioides is being reported here for the first time.
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Zang, Hong Zang Hong. "Part 1, Investigations of DNA damage mechanisms of azinomycin analogs and the natural product leinamycin ; Part 2, Biologically relevant chemical reactions of 1,2-dithiole-3-thiones as cancer preventive agents /." free to MU campus, to others for purchase, 2001. http://wwwlib.umi.com/cr/mo/fullcit?p3036872.
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Hundley, Nicholas James. "Structure Elucidation of Bioactive Compounds Isolated from Endophytes of Alstonia scholaris and Acmena graveolens." Diss., CLICK HERE for online access, 2005. http://contentdm.lib.byu.edu/ETD/image/etd1013.pdf.
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Garcia, Ronald O. [Verfasser], and Rolf [Akademischer Betreuer] Müller. "Exploiting the natural products of novel myxobacteria : phylogenetic and fatty acid perspectives and bioactive compound discovery / Ronald O. Garcia ; Betreuer: Rolf Müller." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2011. http://d-nb.info/1160235104/34.
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Penchev, Petko Ivanov. "Étude des procédés d’extraction et de purification de produits bioactifs à partir de plantes par couplage de techniques séparatives à basses et hautes pressions." Thesis, Toulouse, INPT, 2010. http://www.theses.fr/2010INPT0122/document.
Full textAbstract:
Cette thèse porte sur la mise en œuvre de procédés innovants d'extraction de composés naturels bioactifs de plantes. Nous avons considéré ici l'extraction d'un composé anti-oxydant, l'acide rosmarinique, à partir du végétal mélisse (Melissa officinalis L.), qui contient également d'autres composés d'intérêt (citral et caryophyllène). Différentes techniques d'extraction-purification, soit à haute pression (extraction au CO2 supercritique) ou à pression atmosphérique (extraction Soxhlet, extraction batch, nanofiltration etc.) ont été envisagées. L'objectif de ce travail a été d'étudier expérimentalement l'influence des paramètres opératoires (débit, composition et concentration du solvant, taille des particules, pression et température) sur la cinétique des processus afin de sélectionner les meilleures conditions pour chaque opération. Les résultats expérimentaux ont été ensuite comparés avec plusieurs modèles mathématiques décrivant les phénomènes de transfert de masse et l'écoulement au travers du milieu poreux constitué par la matière végétale broyée. Cette démarche, à partir de la détermination des paramètres physiques du modèle, a fourni les éléments pour une extrapolation potentielle à l'échelle industrielle. Du point de vue du procédé complet d'extraction-purification, l'originalité du travail a été de proposer plusieurs scénarii d'enchainement d'opérations, couplant en synergie des opérations conventionnelles à pression atmosphériques (macération, nano-filtration etc.) et des opérations de traitement au CO2 supercritique avec co-solvantThis thesis deals with the extraction of natural bioactive compounds from plants (case study with Lemon Balm (Melissa officinalis L.)) by using different separation techniques at high (supercritical extraction) and atmospheric pressure (Soxhlet extraction, batch extraction, nanofiltration etc.). The influence of main operational parameters (solvent composition and flow rate, particle size of the raw material, pressure, temperature) on the process kinetics is studied experimentally with the aim to determine appropriate operational conditions for better extraction. The experimental results are confronted to a number of mathematical models in order to estimate the applicability of different theoretical concepts to the particular process and to select and apply appropriate models for determination of important parameters, characterizing the mass transfer process and necessary for scale-up and design purposes. Coupling between different separation methods is also considered and a number of integrated process schemes are proposed resulting in better yield of the targeted compounds
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Wilson, Tyler Aron. "Design and Synthesis of Novel Bioactive Compounds for the Development of HIV-1 Allosteric Integrase Inhibitors, 20S Proteasome Inhibitors, and Anticancer Natural Product Derivatives." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1565967461685907.
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Woods, Katherine B. "Bioactive natural products." Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/26234.
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Montbretins A-E were isolated from the corms of Crocosmia sp., an invasive perennial
plant. The montbretins are inhibitors of human pancreatic α-amylase (HPA). Montbretin A (2-
30) is a competitive inhibitor of HPA with a K₁ of 1.3 nM. The activity of the other family
members varied significantly and provided structure-activity information. Saturation Transfer
Difference (STD) NMR spectroscopy was used to determine that the caffeic acid region of the
montbretins is important for binding. HPA is involved in the breakdown of complex
carbohydrates; inhibition of this enzyme could help with regulation of blood sugar levels after a
meal.
In the lungs of cystic fibrosis patients, the activation of Toll-Like Receptor 5 (TLR5) in
the presence of flagellin leads to inflammation and obstruction. Girolline (3-1), a known
alkaloid, was isolated from a Phonpeian sponge following potent inhibition of the flagellin
initiated TLR5 activation. No activity was observed in any synthetic analogues of girolline. The massacreones are a new family of ecdysteroids isolated from an unidentified Dominican
cnidarian. The extract of the cnidarian had good TLR5 activity, but the massacreones – namely
massacreone A (3-25) and massacreone B (3-26) have only moderate activity and a small
window of activity before they are toxic.
The algal pigment caulerpin (4-29) was isolated from Caulerpa sp. as a compound
showing good activity in a yeast growth restoration assay designed to identify inhibitors ofhuman indoleamine-2,3-dioxygenase (IDO). Caulerpin did not show any activity in a free enzyme IDO assay. IDO is involved in immune escape, which prevents the immunological rejection of tumors.
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Desjardine, Kelsey Lorne. "Bioactive marine natural products." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/31286.
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The chemical exploration of extracts from cultures of the marine bacterial isolate PNG-276 yielded the novel antibiotic tauramamide (2.13), a non-ribosomal peptide active against cultures of Enterococcus sp. and methicillin-resistant Staphylococcus aureus (MRSA). A study of extracts of the marine sponge Spirastrella coccinea yielded the novel macrolide methylspirastrellolide C (3.14), which is active against protein phosphatase 2A (PP2A). A third study examined sponge extracts active in a cannabinoid receptor assay, yielding two known compounds, an A- nor -steroid derivative (4.10) and bengamide A (4.11). Neither purified compound was active in the cannabinoid receptor assay, although in both cases this is the first report of these compounds being isolated from Stylissa massa and Hemiasterella aff. affinis sponges, respectively. [See Thesis for Diagrams]Science, Faculty of
Chemistry, Department of
Graduate
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Zheng, Zehua. "Synthesis of bioactive natural products." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/59815.
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Crude extracts of the rare macrofungus Serpula sp. collected from a wooded area in Sri Lanka showed antimicrobial activity. The novel fungal metabolite serpulanine (2.1) was isolated from the crude extract in very small amounts along with a number of additional secondary metabolites. In order to obtain sufficient quantities of serpulanine (2.1) for biological evaluation, a synthetic route was developed to the natural product and a small library of analogs that have been evaluated in a panel of bioassays. Serpulanine (2.1) inhibits the histone deacetylase I/II with a clear dose response curve. Halitoxins (3.1) that are frequently isolated from marine sponges have a complex macrocyclic chemical structure made of different numbers of monomeric alkylpyridinium units. An unknown halitoxin-related natural product named alotau potently inhibited the dephosphorylation activity of calcineurin. With the goal to elucidate the structure of alotau, compounds of one, two and three pyridinium rings (3.10, 3.7 and 3.8) were synthesized. Though these compounds have NMR spectra similar to the natural alotau, according to bioassay results, none of them recapitulates the activity of the unknown natural product alotau. (+)-Makassaric acid 4.1 was isolated in the Andersen Lab from the marine sponge Acanthodendrilla sp. It showed promising activity in a zebrafish screen for new drugs to treat stroke patients. The convergent synthetic scheme shown below was undertaken to conduct structure activity relationship (SAR) studies. The key intermediate 4.17 has been obtained, and further synthetic efforts will be needed to produce 4.1.Science, Faculty of
Chemistry, Department of
Graduate
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Brastianos, Harry Charilaos. "Bioactive natural products from nature." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/3960.
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Bioassay guided fractionation of a crude extract of the marine sponge
Neopetrosia exigua resulted in the first reported isolation of exiguamines A
and B. These pyrroloquinone alkaloids have an unprecedented hexacyclic
skeleton that has not been previously encountered in natural products. Biological
studies have identified exiguamine A as a potent in vitro inhibitor of the
enzyme indoleamine-2,3-dioxygenase (IDO). IDO is an enzyme expressed by
tumor cells to evade the immune system. Inhibitors against this enzyme may
allow the immune system to attack cancer cells, making this enzyme a potential
drug target for anti-cancer agents.
Investigation of the crude extract of a Bacillus sp. collected in Dominica
led to the isolation of the known diketopiperazine cyclo(S-Val-S-Phe) (3.9). In
vitro biological studies revealed that cyclo(S-Val-S-Phe) is able to promote
neurite outgrowth, even in the presence of physiological inhibitors. In vivo
studies have shown that cyclo(S-VaI-S-Phe) is able promote sprouting in
serotonergic and adrenergic axons. Synthesis of the other three diastereomers
led to the discovery that cyclo(R-Val-R-Phe) is also an in vitro activator of
axonal outgrowth.
Inhibitors of the G2 checkpoint are able to increase the cytotoxicity of DNA
damaging chemotherapeutics. Bioassay guided fractionation of an extract of the
South American plant Duguetia odorata led to the isolation of the G2 checkpoint
abrogator, oliveroline. This investigation also led to the isolation of the
previously unreported alkaloid N-methylguatterine, and the known
alkaloids dehydrodiscretine and pseudopalmatine.
Chemical investigation of the marine sponge Myrmekioderma granulatum
led to the isolation of the new compounds abolenone and myrmekioside C, as well as the known compounds curcudiol, curcuphenol,
abolene and sesquiterpenoid. Biological studies of these
compounds revealed that curcudiol is a ligand of the sex hormone-binding
globulin. This protein is involved in transporting and regulating the
concentration of steroids such as testosterone and estradiol. Many pathological
conditions have a lower plasma concentration of these steroids. Ligands to
SHBG can release steroids into the blood, so this protein is a potential drug
target to treat conditions where a hormone insufficiency is present.
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Li, Guoqiang. "Structure elucidation of bioactive natural products." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0004/NQ29469.pdf.
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Du, Yongle. "Discovery and Delivery of Bioactive Natural Products." Diss., Virginia Tech, 2018. http://hdl.handle.net/10919/83762.
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As a part of search for bioactive natural products from the plants in collaboration with the Natural Products Discovery Institute (NPDI), ten plant extracts were investigated for their antiplasmodial activity against Plasmodium falciparum Dd2 strain. Twenty-eight compounds were isolated, and twelve of them were new compounds. The structures of all these compounds were determined by analysis of their mass spectrometric, 1D and 2D NMR, and ECD spectrum. Among these natural products, there were three compounds with good antiplasmodial activity, trichospirolide A with an IC50 value of 1.5 μM, malleastrumolide A with an IC50 value of 2.7 μM, and (+)-lariciresinol with an IC50 value of 3.7 μM.
In addition to the studies of drug delivery of bioactive natural product, doxorubicin, a novel thiolated doxorubicin analog were designed and synthesized. Its analogs and PEG stabilizing ligands were then conjugated to gold nanoparticles and the resulting Au-Dox constructs were evaluated by TEM. The release of native drug can be achieved by the action of reducing agents, and that reductive drug release gave the cleanest drug release.Ph. D.
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Tang, Shoubin. "Structural and Synthetic Studies of Bioactive Natural Products." Diss., Virginia Tech, 2005. http://hdl.handle.net/10919/26104.
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As part of an ongoing investigation for anticancer agents from natural resources, four plant extracts were determined to contain interesting bioactivity. These extracts were separated by chromatography to afford a number of bioactive compounds that were characterized by spectral analysis.
Fractionation of the fruit extract of Cryptocarya crassifolia led to the isolation of two known flavonoids and two known cryptocaryalactones. Fractionation of the bark extract of the same plant also gave the same two cryptocaryalactones. All these compounds were weakly active in a cytotoxicity assay.
Two new isoflavones were isolated from the roots of an Egyptian lotus plant, Lotus polyphyllos. Both compounds were characterized by UV, NMR, and mass spectroscopic analysis
The methanol extract from the leaves and bark of a Brexiella sp. were found to display significant cytotoxic activity versus the A2780 mammalian cell line. Two highly active cardenolides, glucodigimetholide and xysmalogenin glucoside, were isolated and found to be responsible for the bioactivities. Both compounds were characterized by spectroscopic analysis and comparison to the known literature data.
Two marine extracts were also investigated. The pyridoacridine alkaloids, amphimedine and neoampimedine, were isolated from the marine sponge Petrosia sp., and three bromo-tyrosine alkaloids were isolated from the marine sponge Porphyria flintae. The structures of these known compounds were all elucidated by comparison to literature data.
Two 6-amino-glycoglycerolipids had been previously isolated from a marine algae species and shown to inhibit the activity of the enzyme Myt-1 kinase. These compounds and some related compounds were synthesized and their bioactivities against Myt1 kinase were determined.
Two isotopically labeled paclitaxel analogs (2D, 19F) were prepared in preparation for studies of the tubulin-binding conformation of paclitaxel by REDOR NMR. A new macrocyclic A-nor-paclitaxel was also synthesized, and was found to have good cytotoxicity and improved tubulin-binding activity as compared with paclitaxel.Ph. D.
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Casanova, Martí Àngela. "Action of natural bioactive compounds on the enteroendocrine system." Doctoral thesis, Universitat Rovira i Virgili, 2017. http://hdl.handle.net/10803/460759.
Full textAbstract:
En els últims anys ha augmentat la presència de l’obesitat i de malalties associades a aquesta. En vista d’aquest fet, la cerca de teràpies preventives així com tractaments per aquestes malalties esdevé de gran interès per la salut publica. Les hormones intestinals secretades per les cèl•lules enteroendocrines juguen un paper clau en la regulació de la ingesta i la homeòstasis de la glucosa. En aquest marc, la recerca d’aquesta tesi doctoral s’ha centrat en l’acció dels compostos naturals bioactius sobre el sistema enteroendocrí.
En estudis previs, el nostre grup de recerca va observar que un extracte de proantocianidines del pinyol del raïm (GSPE) augmentava els nivells plasmàtics de GLP-1 en rates. En aquesta tesi doctoral, s’ha esbrinat que aquest augment podria ser en part explicat per l’acció directa del GSPE sobre les cèl•lules enteroendocrines. D’altra banda, s’ha demostrat que l’acció directa del GSPE també modula la secreció de les principals hormones intestinals, induint un augment de la secreció de GIP i PYY, així com una reducció de la secreció de CCK.
Els resultats obtinguts en el cultiu d’organoids han demostrat que el GSPE incrementa els principals marcadors de les cèl•lules L i modula els factors de transcripció involucrats en la diferenciació d’aquestes. Conseqüentment, aquests resultats senyalen que promoure la diferenciació de les cèl•lules L és un mecanisme d’acció del GSPE en tractament prolongats. D’altra banda, la recerca realitzada en tractaments subcrònics ha revelat que el GSPE modifica la composició de la biota intestinal i que el perfil microbià correlaciona amb els paràmetres metabòlics de l’hoste, del qual destaca la correlació amb els nivells plasmàtics incrementats de la hormona GLP-1 activa.
Altrament, s’ha trobat una nova font de compostos naturals bioactius, l’hidrolitzat de pota de pollastre, la qual s’ha demostrat que actua com un agent antihiperglicèmic en rates que presenten una homeòstasis de la glucosa alterada, degut a la capacitat d’inhibir l’activitat de DPP-IV i d’augmentar la secreció endògena de GLP-1.
En conclusió, els resultats obtinguts en aquesta tesi doctoral mostren que els compostos naturals bioactius actuen en el sistema enteroendocrí, per tant aquests podrien ser un agents terapèutics adequats per al tractament de la obesitat i la diabetes.En los últimos años ha aumentado la presencia de la obesidad y de enfermedades asociadas a ésta. Ante este hecho, la búsqueda de remedios preventivos, así como de tratamientos para estas enfermedades, se vuelve de gran interés para la salud pública. Las hormonas intestinales secretadas por las células enteroendocrinas juegan un papel en la regulación de la ingesta y la homeostasis de la glucosa. En este contexto, la investigación de esta tesis doctoral se ha centrado en la acción de los compuestos naturales bioactivos sobre el sistema enteroendocrino. En estudios previos, nuestro grupo de investigación observó que un extracto de proantocianidinas de hueso de uva (GSPE) aumentaba los niveles plasmáticos de GLP-1 en ratas. En esta tesis doctoral se ha descubierto que este aumento podría ser explicado en parte por la acción directa del GSPE sobre las células enteroendocrinas. Por otro lado, se ha demostrado que la acción directa del GSPE también modula la secreción de GIP y PYY, así como una reducción de la secreción de CCK. Los resultados obtenidos en el cultivo de organoides han demostrado que el GSPE aumenta los principales marcadores de las células L y modula los factores de transcripción involucrados en la diferenciación de éstas. Consecuentemente, estos resultados señalan que promover la diferenciación de las células L es un mecanismo de acción del GSPE en tratamientos prolongados. Por otro lado, la investigación realizada en tratamientos subcrónicos ha revelado que el GSPE modifica la composición de la microbiota intestinal y que el perfil microbiano correlaciona con los parámetros metabólicos del huésped, del cual destaca la correlación con los niveles plasmáticos aumentados de la hormona GLP-1 activa. Además, se ha encontrado una nueva fuente de compuestos naturales bioactivos, el hidrolizado de pata de pollo, el cual se ha demostrado que actúa como un agente antihiperglicémico en ratas que presentan una homeóstasis de la glucosa alterada, debido a la capacidad de inhibir la actividad de DPP-IV y de aumentar la secreción endógena de GLP-1. En conclusión, los resultados obtenidos en esta tesis doctoral muestran que los compuestos naturales bioactivos actúan en el sistema endocrino, con lo cual éstos podrían ser unos agentes terapéuticos adecuados para el tratamiento de la obesidad y diabetes.
In the last decade, there has been an increasing prevalence of obesity and metabolic-associated diseases. In view of this fact, finding preventive therapies, as well as treatments for these diseases is of great interest for public health. Gut hormones secreted from enteroendocrine cells (EECs) play a key role in the regulation of food intake and glucose homeostasis. In this context, the research of this thesis has focused on the role of natural bioactive compounds on the enteroendocrine system. Our research group reported in previous studies that grape seed proanthocyanidin extract (GSPE) increased GLP-1 plasma levels in rats. In this thesis, we elucidated that such increase might be in part explained by the direct action of GSPE on enteroendocrine cells. Moreover, we demonstrate that GSPE also modulates the secretion of the main gut hormones by directly acting on EECs, inducing an increase of GIP and PYY release, while reducing CCK release. The results obtained in this thesis using organoids culture demonstrated that GSPE up-regulate the main markers of L-cell and modulate transcription factors involved in L-cell differentiation, and thereby point out that the promotion of L-cell differentiation is a mechanism by which GSPE act in prolonged treatments. Moreover, our findings in mid-term treatments revealed that gut microbiota composition is modulated by GSPE and such microbial composition profile correlates with host metabolic parameters, and remarkably with increased active GLP-1 plasma levels. Furthermore, we found a new source of natural bioactive compounds, chicken leg hydrolyzate, and demonstrated that it acts as antihyperglycemic agent in disrupted-glucose homeostasis animals due to the capacity of inhibiting DPP-IV activity and enhancing endogenous GLP-1 release . In conclusion, the findings obtained in this thesis show that natural bioactive compounds act through different mechanisms on the enteroendocrine system, and thereby could be good therapeutic agents to treat obesity and glucose homeostasis disruption.
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Costa, Elisabete Valente da. "High value-added products from macroalgae: lipids as bioactive compounds." Doctoral thesis, Universidade de Aveiro, 2018. http://hdl.handle.net/10773/22884.
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Doutoramento em Química SustentávelMarine macroalgae are considered to be interesting for food in Western countries and an important supply of novel natural bioactive compounds. Among these are polar lipids such as glycolipids, betaine lipids and phospholipids recognized as high valued lipids for nutrition and as functional ingredient with recognized health benefits. Its biosynthesis depends on several environmental factors such as seasonality, nutrition and habitat, increasing the structural complexity of macroalga lipidome, so that its identification is a current challenge. Mass spectrometry (MS) is a promising tool successfully applied in the study of lipidomic signature of distinct organisms, which can be extended to identify the hundreds of species in the lipidome of macroalgae, and allow them to finally be explored as potential source of lipids. In this work we aim to identify the lipidome of macroalgae representative of Chlorophyta (Codium tomentosum), Rhodophyta (Gracilaria sp. and Porphyra dioica) and Ochrophyta (Fucus vesiculosus). These algae thrive in the Portuguese coast but are recently being cultivated on an integrated multitrophic aquaculture system (IMTA). The characterization of the lipidome will be performed by using mass spectrometry analysis tools coupled to chromatographic methods. We aim to evaluate the bioactive properties of the polar lipids from macroalgae fostering the potential application of these compounds in function of its biological properties as anti-inflammatory and antiproliferative/antitumor agents. The main goals of this project were achieved after the characterization by using HILIC–MS and MS/MS approaches of the lipid extracts carrying on different extraction protocols. The results of this study allowed to identify about 238 molecular species distributed by twelve classes in the macroalgae Codium tomentosum, 147 molecular species in fourteen classes in Gracilaria sp., 110 molecular species in fourteen classes in Porphyra dioica and 181 molecular species distributed by seventeen classes in Fucus vesiculosus. Overall, the lipidome of these macroalgae included GLs monogalactosyl diacylglycerol (MGDG), digalactosyl diacylglycerol (DGDG), sulfoquinovosyl diacylglycerol (SQDG) and its lyso-form (SQMG); phosphatidylcholine (PC) and lyso-PC, phosphatidylglycerol (PG), lyso-PG (LPG), phosphatidic acid (PA), phosphatidylinositol (PI) and betaines (diacylglyceryl trimethyl-homoserine, DGTS). Green macroalgae may be differentiated by the predominance of molecular species including C16 – C20, polyunsaturated fatty acids (PUFA) such as 16:3, 18:3 and 20:5 from n-3 FA family. It contains several molecular species belonging to GLs and betaines including monoacylglyceryl trimethylhomoserine (MGTS), never reported before in the lipidome of macroalga. Red macroalgae are differentiated by molecular species that incorporate C20 FA chains of n-3 and n-6 families, mainly reflected on the composition of GLs.
As macroalgas vermelhas diferenciam-se pelo elevado número de espécies moleculares que incluem cadeias de ácidos gordos C20 da família n-3 e n-6, principalmente na composição dos GLs, e pela presença das classes fosfatidiletanolamina (PE) e inositolfosfoceramida (IPC), apenas identificada nestas algas, pelo que podem ser consideradas um biomarcador deste filo. Neste trabalho, foi avaliada a variação na assinatura lipidómica em duas fases do ciclo de vida (gametófita e esporófita) tomando como alga de estudo a Porphyra dioica. Os resultados obtidos indicaram variações a nível molecular nas classes PC, PA, PE e PG. Em ambas as fases não se observam variações na assinatura dos GLs. O estudo do perfil em ácidos gordos desta alga mostrou que ambas as fases contêm ácidos gordos do tipo 20:4(n-6) e 20:5(n- 3), pelo que apresentam elevado valor nutricional. Na composição da macroalga castanha Fucus vesiculosus, as espécies moleculares combinam diversos ácidos gordos polinsaturados com 18 e 20 átomos de carbono da família n-3 (18:3, 18:4 e 20:5), e 20:4 da família n-6. As algas castanhas apresentam várias espécies moleculares na categoria das betaínas nomeadamente a classe diacilglicerol trimetil-β-alanina (DGTA) e a sua forma liso MGTA, identificada pela primeira vez no lipidoma de macroalgas, ambas não detetadas no lipidoma dos restantes filo. O efeito da sazonalidade na variação da assinatura lipidómica foi estudado para a Fucus vesiculosus colhida em duas estações do ano: inverno e primavera. Os resultados obtidos mostram que o lipidoma desta macroalga mantém o mesmo número de espécies moleculares em todas as classes de lípidos polares, observando-se um aumento da abundância relativa das espécies moleculares que combinam ácidos gordos polinsaturados C18 e C20 (18:3, 18:4, 20:4 e 20:5), em especial nas categorias GLs e betaínas na macroalga de inverno. Assim, podemos concluir que a sazonalidade tem efeito no lipidoma, manifestado pelo aumento de ácidos gordos incorporados nos lípidos polares na macroalga de inverno, muito benéfico em termos nutricionais. Quanto à bioprospecção, avaliaram-se as atividades antiinflamatória e antiproliferativa do extrato lipídico total da macroalga Gracilaria sp.. A atividade anti-inflamatória foi avaliada pela capacidade de inibição dos extratos na produção de NO em macrófagos RAW 264.7 estimulados com o lipopolissacarídeo bacteriano e a atividade anti proliferativa foi testada quanto à capacidade inibitória na proliferação de células T-47D, originadas a partir de um carcinoma ductal humano (cancro da mama) e de células 5637 originadas a partir do carcinoma humano da bexiga. Os extratos totais demonstraram atividade anti-inflamatória e antiproliferativa, pelo que se avaliou o efeito do extrato rico em glicolípidos e a capacidade inibitória na proliferação de células T-47D, verificando-se uma capacidade inibitória da mesma ordem obtida para o extrato total, pelo que poderão ter particular interesse como fitoquímicos. Assim, os resultados obtidos podem contribuir para a valorização das macroalgas como fonte natural e renovável de alimentos, tendo em consideração o valor nutricional como fonte de ácidos gordos n-3 e n-6, e de compostos bioativos a ser utilizados como ingredientes funcionais, fitoquímicos e noutras potenciais aplicações na indústria alimentar e farmacêutica.
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Pereira, Alban R. "Marine natural products : synthesis and isolation of bioactive analogues." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/7526.
Full textAbstract:
Tauramamide (2-12), a linear acylpentapeptide recently isolated from cultures of
Brevibacillus laterosporus (PNG-276) collected in Papua New Guinea, was synthesized in 9
steps and 29% overall yield. Besides confirming the proposed structure, synthetic (2-12)
allowed the antimicrobial assessment of this novel antibiotic. Additionally, a new analogue of
the surfactin depsipeptides family named dealkylsurfactin (2-48), was prepared in 10 steps and
14% overall yield. The compound was employed as a biological tool in binding studies between
the mitotic regulator isomerase Pinl and the microtubule-associated protein tau, a crucial
interaction involved in Alzheimer's disease.
Chemical exploration of Garveia annulata, a seasonal hydroid collected in Barkley
Sound, British Columbia, led to the isolation of twelve secondary metabolites including four new
compounds (3-53 to 3-56). Nine of these metabolites showed inhibition of indoleamine 2,3-
dioxigenase (IDO), with the annulins among the most potent in vitro IDO inhibitors isolated to
date. IDO plays a central role in immune escape, which prevents the immunological rejection of
tumors or the allogeneic fetus.
The ceratamine inspired antimitotic agent (4-142) and inactive analogue (4-157) were
synthesized in no more than 8 steps, with overall yields of 20% and 15% respectively. Activity
evaluation of these analogues suggested that potency improves with planarity and that the
synthetically laborious imidazo[4,5,d]azepine core heterocycle of ceratamines is not required for
activity.
Haplosamate A (5-62), isolated from the marine sponge Dasychalina fragilis collected in
Papua New Guinea, was found to be the first member of a new family of cannabinoid-active
sterols. Saturation transfer double-difference (STDD) NMR experiments confirmed that (5-62)specifically binds the cannabinoid human receptors CB1 and CB2 via the classical cannabinoid
pharmacophore.
A growing appreciation of the therapeutic potential of PI3K inhibitors has encouraged the
development of new inhibitory compounds with enhanced potency, selectivity and
pharmacological properties. Such substances are destined to the treatment of inflammatory and
autoimmune disorders as well as cancer and cardiovascular diseases. An optimization program
intended to develop more stable and isoform-selective PI3K inhibitors based on the marinederived
natural product liphagal (6-1), led to the preparation of a small library of synthetic
analogues.
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Daoust, Julie. "Isolation and structure elucidation of bioactive marine natural products." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/37536.
Full textAbstract:
Clionamines A-D (2.6-2.9) are new aminosteroids isolated from South African specimens of the sponge Cliona celata. All four compounds (2.6-2.9) are activators of autophagy in MCF-7 cells. Autophagy is a catabolic process that plays an important role in maintaining cellular homeostasis. Autophagy is also directly involved in the removal of bacterial and viral antigens and in the development of cancerous tumors.
The novel sesterterpenoid ansellone A (3.4) was isolated from the nudibranch Cadlina luteomarginata and was later found to have been sequestered by the nudibranch from the sponge Phorbas sp. Ansellone A (3.4) is an activator of the cAMP signalling pathway. Following the isolation of 3.4, the novel sesterterpenoids ansellones B-D (4.3-4.5) as well as alotaketal E (4.6) were isolated from the sponge Phorbas sp. and were found to also be activators of the cAMP signalling pathway.
Several bacterial isolates were obtained from the sponge Phorbas sp. in order to investigate the possibility that the ansellones and the alotaketals isolated from this sponge were biosynthesized by a bacterial symbiont. Since these sesterterpenoids were activators of the cAMP signalling pathway, the investigation was conducted using bioassay guided fractionation of the bacterial isolates. The new meroterpenoid phorbasolic acid (5.1) was isolated, but no sesterterpenoids were found in the bacterial isolates.
In an effort to identify molecules with antibiotic properties, a biological assay was designed to screen for inhibitors of the citrate synthase type II enzyme. One aspect of this enzyme that is of therapeutic interest is that Gram-negative bacteria possess a very different isoform of the enzyme than Gram-positive bacteria and eukaryotes. Therefore, an antibiotic specific to type II citrate synthase would target Gram-negative bacteria selectively. An extract from a culture of Bacillus pumillus inhibited the enzyme in the assay. Although the molecule responsible for this effect has yet to be identified, the new aliphatic amide 12-methyl tridecanamide (6.1) was isolated.
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Clement, Jason Anderson. "Studies of Bioactive Natural Products and Mechanism-Based Bioassays." Diss., Virginia Tech, 2005. http://hdl.handle.net/10919/29879.
Full textAbstract:
An extract of the sponge Rhabdastrella globostellifera was active in an assay measuring stabilization of the binding of DNA with DNA polymerase β. From this extract, four isomalabaricane triterpenoids were isolated and characterized, three of which were active in the binding assay. All compounds were active in the A2780 ovarian cancer cell line assay.
Bioassay-guided fractionation of an extract of a sponge of species Dysidea using the A2780 bioassay yielded the known scalarane sesterterpenoid heteronemin in good yield. Four derivatives of heteronemin were prepared semisynthetically from the natural product, tested for their bioactivity, and their structure-activity dependence was observed.
Bioassay guided-fractionation of an extract of a Tuemoya sp. green alga, using an assay for inhibitors of the enzyme Tie2 kinase, afforded a two sulfated cycloartanol triterpenoids. Both the major and minor compounds were identified by spectroscopic methods.
Bioassay-guided fractionation of an extract of Petalonyx parryi yielded three known oleanane triterpenoids which inhibited the lyase domain of DNA polymerase β. The structures were confirmed by NMR spectroscopic techniques. This is the first reported study of the chemical components of Petalonyx parryi.
As part of our antitumor natural product drug discovery efforts, several extracts were selected for bioassay-guided fractionation based on their activity in initial in vitro screens. A new dereplication method using aminopropyl SPE cartridges was applied to six of these extracts, and four of the extracts were dropped due to the presence of long-chain fatty acids (LCFAs). We present results for the testing and application of this SPE-based method for LCFA dereplication.
The cell cycle kinase Chk1 is an interesting target for the development of agents which might potentiate DNA damaging agents. Typical assays for Chk1 involve the use of expensive or radioactive reagents. To facilitate the development of new assays using shorter peptide substrates, small libraries of peptides have been synthesized and tested for their activity as Chk1 substrates. Several of the substrates synthesized displayed activity in the Chk1 assay.
Ph. D.
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Stapleton, Bronwin Louise. "Structural studies of bioactive natural products from marine invertebrates /." St. Lucia, Qld, 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16452.pdf.
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Corrêa, Joze Aparecida Marciano. "Estudo químico de extratos de plantas da família Solanaceae com atividade a fungos fitopatogênicos." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/11/11138/tde-29042015-103758/.
Full textAbstract:
A biodiversidade brasileira é conhecida devido a sua riqueza de espécies, sendo considerada uma fonte promissora de produtos naturais. Dentre as plantas vasculares, a família Solanaceae A. Juss. (Solanaceae) é considerada uma das maiores, apresentando distribuição em todas as regiões tropicais e temperadas do mundo. A família Solanaceae apresenta alta diversidade de espécies de importância econômica como fonte de alimentos, propriedades medicinais e ornamentais. Plantas desta família são fontes de metabólitos secundários de diversas classes químicas com as mais diversas aplicações. Fungos fitopatogênicos são responsáveis por causar diversas doenças e consideráveis perdas na agricultura. O controle das doenças é realizado através de métodos químicos, físicos e biológicos, porém o uso excessivo e ininterrupto de produtos químicos pode resultar na seleção de micro-organismos resistentes. Além disto, muitos fungicidas apresentam toxicidade alta e a sua utilização indiscriminada pode causar efeitos indesejáveis sobre outros organismos no ambiente. O objetivo deste estudo é explorar o potencial biológico e químico de metabólitos secundários produzidos por plantas da família Solanaceae com potencial fungitóxico a fitopatógenos. Foram selecionadas 15 espécies de plantas da família Solanaceae que tiveram os extratos de suas folhas avaliados em ensaios biológicos in vitro sobre o crescimento micelial de 6 fitopatógenos de importância na agricultura. Dentre estas, três foram selecionadas para uma investigação mais aprofundada, as espécies Solanum americanum, Acnistus arborescens e Physalis peruviana. No estudo da planta S. americanum, foram identificados compostos bioativos pertencentes à classe dos glicoalcalóides, que inibiram o crescimento micelial do fitopatógeno Moniliophthora perniciosa. No estudo de A. arborescens foi identificado a presença de um composto ativo pertencente à classe dos vitanolidos, provavelmente o 7β-acetoxivitanolido D, e sua ação antifúngica está sendo relatada pela primeira vez. No estudo da planta P. peruviana a fração semipura bioativa indicou a presença de um composto pertencente à classe dos vitanolidos. Esses resultados evidenciaram que os compostos presentes nas plantas, apresentam bioatividade que inibem o crescimento micelial dos fungos fitopatogênicos Moniliophthora perniciosa e Phytophthora cinnamomi, podendo ser uma nova opção coadjuvante no controle de fitopatógenos.The Brazilian biodiversity is known due to its richness of species, and is considered a promising source of natural products. Among the vascular plants, the family Solanaceae A. Juss. (Solanaceae) is considered one of the largest, with distribution in all tropical and temperate regions of the world. The Solanaceae family has a high diversity of species of economic importance as a source of food, medicinal and ornamental properties. Plants of this family are sources of secondary metabolites from different chemical classes with many different applications. Plant fungi are responsible for causing various diseases and considerable losses in agriculture. The disease control is accomplished through chemical, physical and biological methods, but the excessive and continuous use of chemical products, may result in selection of resistant micro-organisms, in addition, many fungicides have a high toxicity and its indiscriminate use can cause undesirable effects on other organisms in the environment. The objective of this study is to explore the biological and chemical potential of secondary metabolites produced by plants of the Solanaceae family with potential fungitoxic the pathogens. We selected 15 species of Solanaceae plants that had the extracts of its leaves evaluated in vitro biological assays on the mycelial growth of 6 plant pathogens of importance in agriculture. Among these, three were selected for further investigation, the species Solanum americanum, Physalis peruviana and Acnistus arborescens. In the study of plant S. americanum, it was identified bioactive compounds belonging to the class of glycoalkaloids that inhibited the mycelial growth of the pathogen M. perniciosa. In the study of A. arborescens it was identified the presence of the active compound belonging to the class of withanolides, probably the 7β-acetoxywithanolide D, and its antifungal activity is being reported for the first time. In the study of plant P. peruviana semipure bioactive fraction indicated the presence of the compound belonging to the class of withanolides. These results showed that the compounds present in plants, have bioactivity that inhibit the mycelial growth of pathogenic fungi M. perniciosa and P. cinnamomi and may be a new option in the adjuvant control pathogens.
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Fradinho, Patrícia Catarina das Neves Bordalo Branco. "Gluten-free fresh pasta enriched with bioactive compounds." Doctoral thesis, ISA, 2020. http://hdl.handle.net/10400.5/21203.
Full textAbstract:
Doutoramento em Engenharia Alimentar / Instituto Superior de Agronomia. Universidade de LisboaSustainability of the agri-food chain is on today’s agenda, whether through the use of industrial byproducts or the investigation of alternative sources of ingredients. The increasing number of individuals with gluten-related diseases, but also consumers following a gluten-free diet are the drivers for the continually growing number of gluten-free products launched in the market. However, in addition to their still limited commercial availability and high price compared to their wheat counterparts, gluten-free products show nutritional deficiencies. Following the current consumer trends for healthy foods with underlying sustainable principles (ingredients and processes), this thesis aimed the development of a gluten-free fresh pasta based on rice flour from broken grains and Psyllium husk, enriched with Arthrospira platensis, Laminaria ochroleuca and potato peel. Firstly, the gelatinisation (5 – 26%) of rice flour from broken rice (rice processing industry by-product) was performed to assess the optimum conditions for producing gluten-free pasta. Afterwards, the pasta formulation (50% gelatinised rice flour/rice flour) was successfully optimized, and its structure reinforced with 4% Psyllium husk gel. This gluten-free pasta was then enriched with bioactive compound sources (Arthrospira platensis, Laminaria ochroleuca and potato peel) incorporated as lyophilised biomass, gel or liquid extract obtained by subcritical water extraction (autohydrolysis), an eco-friendly technology. The pastas developed were characterized in terms of cooking quality parameters, texture, colour, rheology, nutritional composition, antioxidant activity, in vitro digestibility and sensory analysis. It was found that autohydrolysis was a suitable technology for the valorisation of distinct materials, namely marine and industrial. Pastas with Laminaria ochroleuca provided a high mineral and fibre contents, and low-fat content, so that could bear nutritional claims. On the other hand, Arthrospira platensis incorporation proved to have a positive effect on the pasta antioxidant activity and overall sensory analysis without affecting the in vitro digestibility. Pasta with potato peel extract presented a high total phenolic content and antioxidant activity. All formulations presented good overall cooking quality and texture and rheology properties
N/A
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Borisova, Ralitsa Bogomilova. "Isolation of a Rhodococcus Soil Bacterium that Produces a Strong Antibacterial Compound." Digital Commons @ East Tennessee State University, 2011. https://dc.etsu.edu/etd/1388.
Full textAbstract:
Rhodococci are notable for their ability to degrade a variety of natural and xenobiotic compounds. Recently, interest in Rhodococcus has increased due to the discovery of a large number of genes for secondary metabolism. Only a few secondary metabolites have been characterized from the rhodococci (including 3 recently described antibiotics). Twenty-four new Rhodococcus strains were isolated from soils in East Tennessee using acetonitrile enrichment culturing and identified using 16S rRNA analysis. Forty-seven Rhodococcus strains were screened for antibiotic production using a growth inhibition assay. One strain, MTM3W5.2, had 90% similarity to the Rhodococcus opacus 16S rRNA gene sequence and produced a large zone of inhibition against R. erythropolis and a large number of closely related species. The antimicrobial compound produced by MTM3W5.2 had a large MW of 911.5452 Da and acts much like a bacteriocin but no amino acids were detected in this molecule based on TLC analysis.
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Yan, Luping. "Bioactive marine natural products : analogue synthesis, SAR, and target identification." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/50069.
Full textAbstract:
3,6,7-trihydroxycoumarin C11 (2.14) was first isolated from the green alga Dasycladus vermicularis in 1983. C11 and 3,7,8-trihydroxycoumarin C21 (2.15), alongside their precursors C12 (2.18) and C22 (2.20), were synthesized for a target-based screen for anti-HCV drugs, where ideal hits eliminate fluorescence signals by inhibiting the proteolytic activity of HCV NS3pro/Pep4A against a synthetic peptide “BS-IQFS”. With C12 and C22 serving as negative controls, C11 and C21 inhibited the NS3pro/Pep4A activity in vitro. The IC₅₀’s of C11 and C21 were 3.07 μM and 2.10 μM, respectively.
A bioassay-guided fractionation identified sintokamides A – E (3.11 – 3.15) from extracts of the sponge Dysidea sp. in 2008. In a phenotypic screen, the chlorinated dipeptides showed strong to modest inhibition of luciferase activity caused by AR NTD transactivation in LNCaP cells. Larger quantities of sintokamides A and B were isolated from the sponge for further biological study. After developing a practical synthetic route, a comprehensive SAR of the sintokamides was available from the in vitro activities of 29 synthetic analogues/precursors based on a 1,17-dinorsintokamide skeleton. LPY26 [(4R,10R)-3.233] showed the best biological activity in the synthetic analogues prepared to date and it was selected as a drug lead. Mechanism of action study using synthetic probes LPY30 (4.7) and LPY31 (4.8) revealed that the hexachlorinated 1,17-dinorsintokamides covalently bound to the AR, but not to the same AF1 region in the AR NTD as EPI-001 (3.8).
The structure of latonduine A (5.1) isolated from the sponge Stylissa carteri and its total synthesis were published in 2003. Later, latonduine A was shown to be active in a phenotypic screen to find drug leads for the treatment of cystic fibrosis caused by the F508del mutation. Latonduine A could efficiently correct immunofluorescent F508del-CFTR trafficking from the endoplasmic reticulum to the plasma membrane in the engineered cells. Synthetic latonduine A and N-biotinylated latonduine A (5.17) were prepared to support biological studies aimed at identifying its cellular protein target(s). These studies culminated in the finding that latonduine A is an inhibitor of PARP-3 with an EC₅₀ of 400 pM in CFBE41o- cells.Science, Faculty of
Chemistry, Department of
Graduate
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Forestieri, Roberto. "Isolation, structure elucidation, and total synthesis of bioactive natural products." Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/45668.
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Almaliti, Jehad S. "Natural Products-Inspired Synthesis and Biological Evaluation of Bioactive Agents." University of Toledo Health Science Campus / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=mco1384555204.
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Wong, Wan Yee. "Solvothermal crystallization of organic compounds and natural products /." View abstract or full-text, 2006. http://library.ust.hk/cgi/db/thesis.pl?CHEM%202006%20WONG.
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Cowe, H. J. de L. "Molecular studies of natural products and related compounds." Thesis, Robert Gordon University, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370758.
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Boot, Claudia M. "Marine-derived fungi : an effective source of novel bioactive natural products /." Diss., Digital Dissertations Database. Restricted to UC campuses, 2007. http://uclibs.org/PID/11984.
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Montgomery, Laura Jane. "Investigations of the biosynthesis and biomimetic synthesis of bioactive natural products." Thesis, University of Warwick, 2008. http://wrap.warwick.ac.uk/4420/.
Full textAbstract:
This thesis describes work towards the biomimetic synthesis and understanding the biosynthesis of two families of natural products: prodiginines and quartromicins. Prodiginines are a large family of red pigmented tripyrrole antibiotics. Although they have not been used clinically, the promising anti-cancer, immunosuppressive and antimalarial activity they display at non-toxic doses has generated renewed interest in their utilisation. The synthesis of an analogue of the proposed pyrrole-2-carboxyl-RedO intermediate in prodiginine biosynthesis has been achieved. The resulting NAC thioester and analogues of it have been used to investigate the prodiginine biosynthetic pathway in Streptomyces coelicolor, and to examine the production of prodiginine analogues by mutasynthesis. Quartromicins, novel anti-viral antibiotics, are a structurally unique group of spirotetronate natural products produced by Amycolatopsis species. They are unusual symmetric macro cyclic compounds which possess a 32-membered carbocyclic structure with four spirotetronic acid units connected by enone or dienone linkers in a head-to-tail fashion. These macrocyclic compounds are intriguing because they have alternating endo- and exo- spirotetronic acid units, with the opposite "comers" being identical. Although the quartromicins have therapeutic potential, very little is known about their biosynthesis. In this research a biosynthetic pathway to the quartromicins has been proposed based on hypothetical pathways to related natural products. The synthesis of the two putative key intermediates in quartromicin biosynthesis has been achieved. An improved method for the synthesis of exomethylene tetronates has been developed, and novel rearrangements have been discovered. The two putative key intermediates have been used to investigate the biomimetic synthesis of the carbon skeleton of the quartromicin algycone, and mass spectrometric evidence for formation of homo- and heterodimers, and a heterotetramer of the key intermediates has been obtained.
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Stevens, Kiri. "Methodology for the synthesis of NP25302 and other bioactive natural products." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:ae18879e-d75e-4280-ba55-1ae08e64034f.
Full textAbstract:
Total synthesis of the pyrrolizidine alkaloid NP25302: (+)-NP25302 is an unusual vinylogous urea containing pyrrolizidine alkaloid shown to exhibit cell adhesion inhibition. It was envisaged that this natural product could be accessed by a novel 5-endo-dig cyclisation to construct the pyrrolizidine core, and a Curtius rearrangement to install the vinylogous urea motif. This methodology was first tested on a model system, furnishing nor-NP25302 from L-proline in 12 steps and 9% overall yield. The total synthesis of (±)-NP25302 was completed in 9 steps and 26% overall yield from ethyl 2-nitropropionate using similar methodology. Studies into the stereospecificity of the Au(I)-catalysed cyclisation of monoallylic diols: During the synthesis of (+)-isoaltholactone in the Robertson group, the key Au(I)-catalysed cyclisation was observed to occur with some stereospecificity. Further investigations were therefore conducted into the stereochemical outcome of this reaction using stereodefined allylic alcohols, and from the combined results a mnemonic was proposed to predict the stereochemistry of the products of this reaction. Studies into the total synthesis of ascospiroketals A and B: Investigations were conducted into the total synthesis of the recently isolated natural products ascospiroketals A and B. A second generation synthesis was used to construct advanced intermediates 1 and 2.
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Berger, John Michael. "Isolation, Characterization, and Synthesis of Bioactive Natural Products from Rainforest Flora." Diss., Virginia Tech, 2001. http://hdl.handle.net/10919/28086.
Full textAbstract:
As part of our ongoing investigations for anticancer drugs from rainforestflora, five plant extracts were determined to contain interesting bioactivity. These extracts were subjected to various separation techniques, affording a number of bioactive compounds that were then characterized by spectral and degradative methods. A methanol extract of Cestrum latifolium Lam. yielded the known compound parissaponin Pb. Hydrolysis afforded its aglycone, the known spirostanol diosgenin. GCMS analysis characterized the derivatized, hydrolyzed sugars.
Previous investigations of Albizia subdimidiata provided two saponins including the new compound albiziatrioside A. The sugar moieties of these two compounds required further characterization. They were characterized by spectral analysis of the partially hydrolyzed products and by GCMS analysis of the hydrolyzed sugars. Pittoviridoside, a saponin from Pittosporum viridiflorum, was isolated in a previous investigation. Further investigation was required to characterize the stereochemical environment of the sugar moiety. The stereochemistries of the pentose sugars were determined by conversion into thiazolidine acetates of known stereochemistries and analysis with standards by GCMS.
Two new diterpenes were isolated from Hymenaea courbaril, which in an earlier investigation provided a new diterpene. The absolute configurations of these diterpenes were assigned on the basis of anisotropic NMR studies, X-ray crystallography, circular dichroism analysis and previously reported literature. A previous investigation of Miconia lepidota isolated two benzoquinones, primin and its n-heptyl analog. Fifteen analogs were synthesized for structure-activity relationship determination. It was found that benzoquinones with moderate-length alkyl side chains displayed the strongest activity in our yeast and cancer cell lines.Ph. D.
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Rapson, Trevor Douglas. "Bioactive 4-methoxypyrrolic natural products from two South African marine invertebrates." Thesis, Rhodes University, 2005. http://hdl.handle.net/10962/d1006766.
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This thesis presents an investigation of the 4-methoxypyrrolic constituents of two South African marine invertebrates, the nudibranch Tambja capensis and the bryozoan Bugula dentata. Three known compounds tambjamine A (7), tambjamine E (13) and the tetrapyrrole (15) were isolated during this investigation. All three compounds were shown to be active against oesophageal cancer in accordance with the general anticancer and immunosuppressive properties observed for 4-methoxypyrrolic natural products. Tambjamine A (7), tambjamine E (13) and the tetrapyrrole (15), together with tambjamine K (21) and L (22) (previously isolated in our laboratory) were used as standards to quantitatively assess the presence of these tambjamines in T. capensis and B. dentata collected from three different sites along the South African coast. This study confirmed that B. dentata is the source of the 4-methoxypyrrolic natural products sequestered by T. capensis and eliminated the closely related bryozoan B. neritina as a source of these metabolites. The paucity of tambjamine L (21) and K (22) obtained in previous investigations of the sequestered chemistry of T. capensis prompted an attempt at the development of synthetic methodology that could be used to synthesize tambjamines in sufficient yield for in depth bioactivity studies. In order to by pass the extensively reported problems associated with the synthesis of this group of compound 3-methoxy-2-formylpyrrole (47), readily accessible from 3-methoxypyridine N-oxide (48), was used as the starting material in a singlet oxygen induced 2,2’ bipyrrole coupling reaction. Although 47 proved unreactive in this coupling reaction, when the N-Boc protected analogue of 47 was used, and the reaction worked up in the dark, the novel methyl 4-aza-5-oxo-6,6-di-(2-pyrrolyl)-2(Z)-hexenoate (57) was obtained in low yield. The physical properties of tambjamine (E) (13) and the tetrapyrrole (15) were investigated to further the understanding of the proposed oxidative DNA cleavage mechanism and to determine the potential of the 4-methoxypyrrolic natural products as photodynamic therapy agents.
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Pérez, Hemphill Catalina Francis [Verfasser]. "Bioactive fungal natural products from extremophilic endophytes / Catalina Francis Pérez Hemphill." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2017. http://d-nb.info/1125595418/34.
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Hagos, Selam. "Chemical Investigation of Bioactive Marine Extracts." Scholar Commons, 2018. https://scholarcommons.usf.edu/etd/7301.
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Natural products have been a fundamental source of medicinal scaffolds for decades; with sixty percent of marketed drugs. Many synthetic chemists are focused on synthesizing potent and nontoxic compounds for pharmaceutical targets, however, nature is still proving to be a source of new bioactive compounds. Produced by the host organism for defense, reproduction and communication, secondary metabolites also demonstrate promising bioactivity against human pathogens. Hence, natural product chemists continue their quest for new leads.
As a continuation of these efforts, this thesis attempts to explore fungi and sponges for new chemistry, and ultimately, new drug candidates. Antarctica is largely untapped; hence herein two Antarctic sponges were chemically investigated. This resulted in isolation and characterization of two metabolites. Concurrently, chemical investigation of fungus, from Floridian mangrove species, resulted in the isolation of two structurally diverse metabolites. Further, a dereplication process was applied to MPLC fractions, which lead to the identification of known metabolites and mycotoxins. This enabled prioritization of fractions for future studies.
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Stout, Elizabeth Paige. "Discovery and synthesis of bioactive natural product probes from marine systems." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/37301.
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Flora and fauna from terrestrial and marine environments provide libraries of natural compounds for drug discovery. The last four decades have seen major advances in ocean exploration that have allowed chemists and biologists to explore previously inaccessible and rare marine organisms. The study of under-explored marine organisms can result in the discovery of structurally novel and unusual natural products with drug potential. Prior to 2005, no natural products had been reported from the Fijian red macroalgae Callophycus serratus or Neurymenia fraxinifolia. As a result of the work described in this thesis and others in the same research group, 33 unique brominated meroditerpenes have been isolated and elucidated alpha-pyrone natural products were discovered from N. fraxinifolia, enriching the natural product library for drug development. Several natural products isolated from C. serratus exhibited sub-micromolar inhibition against the human malaria parasite Plasmodium falciparum, including a drug-resistant strain. Derivatization of the natural product bromophycolide A into fluorescent probes allowed the determination of a non-enzymatic mechanism of action against the human malaria parasite P. falciparum. Through a combination of detailed SAR mapping, molecular fluorescent imaging of live cells, UV-vis spectroscopic analyses, and protein affinity techniques, the mechanism of action of bromophycolide A against P. falciparum was determined to involve inhibition of heme crystallization. These studies identify a new class of natural products that target heme detoxification in both drug-sensitive and drug-resistant P. falciparum and suggest an avenue to circumvent drug resistance.
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Protti, Michele <1986>. "Hyphenated Approaches for the Analysis of Bioactive Natural Compounds in Complex Matrices." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7520/.
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Plants, animals and micro-organisms represent a reservoir of natural products, the so called “natural source-derived compounds”. This is particularly true for the plant kingdom, as it offers a variety of species still used as remedies for several diseases in many parts of the world. Nevertheless, the bioactive potential of many plant species remains largely unexplored. Thus, biodiversity represents an unlimited source of chemical entities with potential beneficial effects on human health. These compounds are usually secondary metabolites often present in low quantity in plant material and their extraction, purification and quantitation still remain a great challenge for analytical scientists.
The research activity carried out during these three years of PhD Programme was focused on the development, validation and application of original methods aimed at the quali-quantitative analysis of compounds with potential bioactive interest in plant matrices, foods, drinks and related products, as well as the analytical screening of plant by-products from cosmetic manufacture. Bioactive substances, belonging to the classes of polyphenols, aminoacids, coumarins, triterpenes and phytohormones, have been investigated as authenticity markers, in order to identify high quality products and to valorise niche products. The study regarded herbs (Argania spinosa), fruits (Citrus × myrtifolia, Punica granatum) and berries (Myrtus communis) mainly used as folk medicines for their broad spectrum of supposed pharmacological and therapeutic effects. The analytical methods developed within this study are based on high performance liquid chromatography and ultra-high performance liquid chromatography coupled to spectrofluorometric detection, triple quadrupole and high-resolution triple quadrupole mass spectrometry (HPLC-F, LC-MS/MS and UHPLC-HRMS). Significant efforts have been put also into the development and optimisation of miniaturised sample pretreatment strategies, such as micro-solid phase extraction (µSPE) and micro-extraction by packed sorbent (MEPS), able to purify complex matrices of natural origin (whole fruits, fruit parts, leaves and their extracts) and derived commercial products.
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Ashour, Mohamed A. A. "Structure elucidation of bioactive marine natural products using modern methods of spectroscopy." [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=982523963.
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