No / Various saponins, plant glycosides with favorable anti-tumorigenic properties, have been used to inhibit tumor cell growth by cell cycle arrest and apoptosis with IC50 values of up to 0.2 μM. We describe several groups of saponins (dioscins, saikosaponins, julibrosides, soy saponins, ginseng saponins and avicins) currently investigated for their use in tumor therapy. We focus on cellular and systemic mechanisms of tumor cell growth inhibition both in vitro and in vivo, combinational approaches with saponins and conventional tumor treatment strategies, and successful syntheses of saponins. The increasing interest in saponins for tumor therapy is very promising for the future development of sophisticated anti-cancer drugs.

No description available.

No description available.

Mogrosides, the main active components in S. grosvenorii SWINGLE, are considered to be some 250 times sweeter than sucrose and to possess several medicinal attributes. Previous isolation processes used large quantities of toxic solvent that resulted in toxic residues of organic solvent in this high value food. Supercritical fluids fulfill the requirements of non-toxicity, recycle ability, and useful solvent characteristics. The work presented in this thesis is directed to the extraction of mogrosides from the powdered S. grosvenorii concentrate (SG) and the crude extract after resin treatment (MG) with sub critical water and supercritical CO2. / Because no source of mogroside V reference material is available commercially, the first objective of this research was to isolate mogroside V of sufficient purity that it could be crystallized. This objective was achieved by selecting suitable eluates from resin chromatography coupled with preparative thin layer chromatography (TLC). Crystalline white isolate was further characterized by 13C-NMR and by MS and determined to be mogroside V, which was suitable as a reference material for subsequent experiments. / The process variables for both sub critical water and supercritical carbon dioxide extraction were evaluated and optimized so that conclusions could be formulated regarding the relative merits of the two proposed extraction methods. The efficiency of extraction was determined spectrophotometrically based on the recovery of mogrosides from the starting material following the vanillin-HClO4 method. / When compared with Soxhlet solvent extraction, supercritical fluid extraction with either sub critical water or supercritical CO2 provided improved recoveries and consumed less organic solvent. In addition, the purity of the extracts differed greatly. For identical SG samples, sub critical water extraction was demonstrated to be more efficient (62.4% recovery) compared with 37.0% recovery by EtOH modified scCO2 extraction or 5.1% for Soxhlet extraction with hexane.

Chemoreception plays an important role in predator-prey interactions and feeding dynamics. While the chemoreception of attractant or pleasant tasting compounds has been well studied, aversive chemoreceptive signaling has been difficult to investigate behaviorally in an ecological context because these interactions are species- and context- specific and deterrent compounds vary among prey. Using the coral reef system, this thesis explores on a molecular level the deterrent mechanism underlying detection by fish predators of an aversive compound, in order to gain a greater understanding of predator-prey interactions in this community. Like other organisms that are sessile or slow-moving, marine sponges have special mechanisms for defense from predation, commonly containing aversive-tasting compounds that defend these organisms from predation. To this end, we sought to identify and characterize a fish chemoreceptor that detects one or more of these compounds. We isolated a single cDNA clone encoding RAMP-like triterpene glycoside receptor (RL-TGR), a novel co-receptor involved in the signaling of triterpene glycosides. This co-receptor appears to be structurally and functionally related to receptor activity-modifying proteins (RAMPs), a family of co-receptors that physically associate with and modify the activity of G protein-coupled receptors (GPCRs). Expression in Xenopus oocytes showed that it responds to triterpene glycosides in a receptor-mediated manner and requires co-expression of a GPCR to enable signaling in oocytes; both of these receptors may be components of a larger signaling complex. A 40 bp portion of the gene is conserved across multiple fish species, but is not found in any other organism with a sequenced genome, suggesting that the expression of this receptor is limited to fish species. RL-TGR is the first identified gene encoding a co-receptor that responds to a chemical defense. This finding may lead the way for the identification of many other receptors that mediate chemical defense signaling in both marine and terrestrial environments, as this protein has the potential to represent the first of an entire family of co-receptors that respond to aversive compounds.

Submitted by Alisson Mota (alisson.davidbeckam@gmail.com) on 2015-07-16T19:59:52Z No. of bitstreams: 1 Dissertação - Willian Hayasida.pdf: 20367139 bytes, checksum: 7bb94fab5a8c140d16b312d8b014111c (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2015-07-17T18:48:45Z (GMT) No. of bitstreams: 1 Dissertação - Willian Hayasida.pdf: 20367139 bytes, checksum: 7bb94fab5a8c140d16b312d8b014111c (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2015-07-17T18:52:28Z (GMT) No. of bitstreams: 1 Dissertação - Willian Hayasida.pdf: 20367139 bytes, checksum: 7bb94fab5a8c140d16b312d8b014111c (MD5) / Made available in DSpace on 2015-07-17T18:52:28Z (GMT). No. of bitstreams: 1 Dissertação - Willian Hayasida.pdf: 20367139 bytes, checksum: 7bb94fab5a8c140d16b312d8b014111c (MD5) Previous issue date: 2011-07-01 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The Meliaceae family comprises has about 50 genus and approximately 700 species, generally arboreus, occurring in regions Pantropical. The predominant metabolites in the family are triterpenoids with cycloartane, dammarane, tirucallane and apotirucallane skeleta, further degraded triterpenoids (limonoids and steroids). The genus Guarea possesses about 50 species however chemical studies are limited to ten species, whose reports are sesquiterpenes, diterpenes and triterpenes (cycloartane, tirucallane lanostane and apotirucallane), further limonoids. Although the occurrence of approximately 30 species of Guarea in Amazon have few relates on chemical studies, this acted as stimulus for our investigation about Guarea convergens T.D. occurrent in Amazon. Thus, leaves and branches collected in the Adolpho Ducke Forest Reserve were submitted to maceration to obtain the organic extracts. The chromatographic fractionning of the CH2Cl2 and MeOH leaves extracts led to the isolation of apotirucallane triterpenes: the 24R-acetoxy,25-hydroxy-3,7-dioxo-apotirucalla-14-en-21,23- olide (1) and the 7a,24R,25-trihydroxy-3-oxo-apotirucalla-14-en-21,23-olide (4), steroids: ergosta-5,24-diene-3 ,4 ,22S-triol (2) and ergosta-5,24-diene-3 ,7 -21-triol (3). The compounds 1, 3 and 4 are being reported for first time. The CH2Cl2 branches extract yielded a mixture of steroids (b-sitosterol and stigmasterol, 5) and the tirucallane triterpenes namely melianone (6) and melianodiol (7). This is the first chemical study effected with species G. convergens whose isolated and identified compound provide contributions to knowledge of the chemosystematic of the Rutales order. / A família Meliaceae possui cerca 50 gêneros e aproximadamente 700 espécies, geralmente arbóreas de ocorrência nas regiões Pantropicais. Os metabólitos predominantes na família são os triterpenos com esqueletos cicloartano, damarano, tirucalano e apotirucalano além dos triterpenos degradados (limonóides e esteróides). O gênero Guarea apresenta cerca de 50 espécies, no entanto os estudos químicos são limitados a dez espécies cujos relatos são de sesquiterpenos, diterpenos e triterpenos (cicloartano, tirucalano, lanostano e apotirucalano), além dos limonóides. Apesar da ocorrência de aproximadamente 30 espécies de Guarea no Amazonas, existem poucos relatos sobre os estudos químicos, o que nos estimulou a seleção de G. convergens ocorrente no Amazonas. Assim, folhas e galhos coletados na Reserva Florestal Adolfo Ducke foram submetidos à maceração para obtenção dos extratos orgânicos. O fracionamento cromatográfico dos extratos CH2Cl2 e MeOH de folhas resultou no isolamento dos triterpenos com esqueleto apotirucalano, 24R-acetoxi-25-hidroxi-3,7-oxoapotirucala- 14-en-21,23-olideo (1) e 7a,24R,25-trihidroxi-3-oxo-apotirucala-14-en-21,23- olideo (4) e dos esteróides do tipo ergostano, ergosta-5,24-dieno-3 ,4 ,22S-triol (2) e ergosta-5,24-dieno-3 ,7a,21-triol (3). As substâncias 1, 3 e 4 estão sendo relatadas pela primeira vez. Nos extratos dos galhos, além de -sitosterol (5) foram isolados os triterpenos do tipo tirucalano, melianona (6) e melianodiol (7). Esse é o primeiro estudo químico da espécie G. convergens cujos compostos isolados e identificados fornecem contribuições para o conhecimento da quimiossistemática da ordem Rutales.

The natural product celastrol (1) possesses a wide array of promising biological activities related to diseases characterized by protein misfolding including those associated with neuronal degradation, inflammation, and cancer. Relevant to cancer, celastrol functions as a non-ATP-competitive inhibitor of heat shock protein-90, providing a potential lead for the development of new inhibitors with improved pharmacology. A laboratory preparation of the small molecule was undertaken to provide access to the unnatural enantiomer of celastrol. The lack of understanding of the chemistry and biology of the growing class of celastroids is attributed to the incompatibility of biologically inspired polyene cyclization strategies to assemble friedelin triterpenoids. As a result of these problems residing at the interface of chemistry and biology, a purely synthesis-based strategy for polyene cyclizations to rapidly construct the pentacyclic core of the friedelin and celastroid natural products has been developed. This efficient strategy is gram scalable culminating in the first total synthesis of wilforic acid (127) and an advanced intermediate capable of delivering celastrol (1) as well as numerous celastroid natural products. Phenols possess broad utility serving as key materials in all facets of chemical industries, especially the pharmaceutical industry. The ideal synthesis of a phenolic compound entails the direct oxidation of an aryl C-H bond remains to be a difficult synthetic challenge. Following our initial report describing the hydroxylation of arenes using phthaloyl peroxide, new peroxide derivatives were investigated to probe their reactivity in an effort to hydroxylate aromatics which were previously unreactive. Electronically poor to moderately rich arenes were successfully hydroxylated with a broad functional group tolerance using 4,5-dichlorophthaloyl peroxide. This protocol has been applied toward the rapid synthesis of phenolic analogs and metabolites of current pharmaceuticals as well as biocides. Mechanistic studies using kinetic isotope effect, competition, and benzylic oxidation experiments indicate that a novel diradical reverse-rebound mechanism is the likely pathway. Further examination of the transition-state using linear free energy relationships with sigma vs. sigma+ values established a linear trend with a low negative rho value (- 3.92) corresponding best using sigma values supporting a diradical reverse-rebound addition. / text

No description available.

L’intérêt des substances d’origine naturelle, potentiellement anti-tumorales nous a amené à nous intéresser aux saponines triterpéniques et stéroïdiques de plantes issues de la biodiversité africaine de la famille des Araliaceae et des Dracaenaceae. En effet, des études antérieures menées sur quelques plantes de ces deux familles ont conduit à l’obtention de molécules complexes et originales possédant d’excellentes propriétés cytotoxiques, immuno-modulatrices, anti-inflammatoires. Au vu de ces résultats nous avons entrepris des investigations pharmaco-chimiques sur Cussonia arborea (Araliaceae), Dracaena deisteliana et Dracaena arborea (Dracaenaceae), plantes médicinales couramment utilisées en pharmacopée traditionnelle africaine pour traiter différentes maladies. Les travaux menés ont conduit à l’isolement de 31 composés purs en utilisant les différentes techniques analytiques du laboratoire notamment les diverses techniques de chromatographie liquide successive à pression atmosphérique, moyenne pression et flash chromatographie sur silice en phase normale et en phase inverse. Les structures ont été déterminées par les méthodes de spectrométrie de masse en source FAB et de spectroscopie de RMN 1D et 2D (COSY, TOCSY, NOESY, HMBC et HSQC). Parmi les 07 composés purs obtenus des écorces de Cussonia arborea, 5 sont des nouvelles saponines triterpéniques dont un dérivé de l’acide ursolique, un dérivé de l’hédéragénine et trois dérivés de l’acide oléanolique, tous disubstitués en position 3 et 28 par des chaînes oligosaccharidiques. 13 composés purs sont obtenus à partir des feuilles de Cussonia arborea, dont 7 nouvelles saponines triterpéniques dérivés de l’acide ursolique, de l’acide 23-hydroxyursolique, de l’hédéragénine et de l’acide oléanolique dont 04 d’entre elles sont obtenues sous forme de mélanges inséparables d’isomères acide oléanolique/acide ursolique et hédéragénine/acide 23-hydroxyursolique. A partir des écorces de Dracaena arborea et des tiges de Dracaena deisteliana, nous avons isolé et caractérisé 10 saponines stéroïdiques dont 4 nouvelles et une sapogénine. Les activités de certains de ces produits purs ont été évaluées sur deux lignées de cellules cancéreuses coliques humaines HCT 116 et HT-29. / The interest of the substances from natural origin, potentially antitumor led us to interest in triterpenoid and steroidal saponins of plants from the African biodiversity belonging to the Araliaceae and Dracaenaceae families of plants. Indeed, of the former studies undertaken on some plants of these two families led to obtaining complex and original molecules having excellent cytotoxic, immuno-modulating, anti-inflammatory properties. Within sight of these results we undertook pharmaco-chemical investigations on Cussonia arborea (Araliaceae), Dracaena deisteliana, and Dracaena arborea (Dracaenaceae), medicinal plants usually used in african traditional pharmacopeia to treat various diseases. The work led to the isolation of 31 pure compounds by using the various analytical techniques in particular the various chromatography techniques (CC, MPLC, TLC, flash) on silica gel, normal and reversed phases. The structures were determined by the methods of mass spectrometry (FAB, ESI, IE) and 1D (1H and 13C) and 2D (COSY, TOCSY, NOESY, HMBC and HSQC) NMR spectroscopy. Among the 07 pure compounds obtained of the barks of Cussonia arborea, 5 are new triterpenoid saponins derivatives of ursolic acid, hederagenin and three derived from the acid oleanolic, all disubstituted in position 3 and 28 by oligosaccharidic chains. 13 pure compounds were obtained from leaves of Cussonia arborea, seven of which are new triterpenoid saponins derivatives of oleanolic acid, ursolic acid, hederagenin and 23-hydroxyursolic acid of which four were obtained as mixtures of isomers oleanolic acid/ursolic acid and hederagenin/23-hydroxyursolic acid. From the bark of Dracaena arborea and stem of Dracaena deisteliana, we isolated and characterized ten steroidal saponins including 4 new and sapogenin. The activities of some of these pure products were evaluated on two cancerous lines human colic cells HCT 116 and HT-29.

No description available.