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Squalene is a natural triterpene that has many applications in the pharmaceutical, cosmetic and food industry. The current production of this natural substance is problematic, as deep sea sharks are hunted for its extraction from shark liver oil. Extraction from certain lipid-rich plants is possible, but requires large amounts of land, is seasonal and runs the risk of competing with food production. Therefore, this work deals with an alternative approach: The biotechnological squalene production by marine eukaryotes belonging to the thraustochytrid family. Thraustochytrids are unicellular eukaryotes that occur in marine habitats and are able to produce large amounts of lipids and store them in their cells. The proportion of squalene in the total lipid depends heavily on the chosen cultivation conditions. In this work, the influence of oxygen-limiting conditions on the growth and squalene productivity of the wild-type Schizochytrium sp. S31 was investigated. For this purpose, the organism was cultivated in shake flasks and in a bioreactor using different cultivation strategies. Respiratory activity was monitored in both cultivation systems by analyzing the gas composition of the exhaust gas or the headspace in real time. During fed-batch cultivation under oxygen-limiting conditions, a squalene yield of 1.1 g/L was achieved. With the aim of a more cost-effective biotechnological production of squalene and the development of a circular process, the second part of this work dealt with the use of potential side streams as medium substitutes. The complex nitrogen source of the cultivation medium used for thraustochytrids was successfully replaced by biomass from the cultivation of the basidiomycete Pleurotus ostreatus. An extract rich in nitrogen sources was produced from the fungal components, especially the fungal mycelium, by enzymatic hydrolysis. The clarified extract was then used to cultivate the thraustochytrid Schizochytrium sp. S31 and its influence on growth and, Squalen ist ein natürliches Triterpen, welches vielfältige Anwendung in der Pharma-, Kosmetik- und Lebensmittelindustrie findet. Die derzeitige Produktion dieses Naturstoffes ist problematisch, da für seine Gewinnung aus Haifischleberöl Tiefseehaie bejagt werden. Die Extraktion aus bestimmten lipidhaltigen Pflanzen ist möglich, benötigt aber viel Land, ist saisonabhängig und läuft in Gefahr, mit der Nahrungsmittelproduktion zu konkurrieren. Diese Arbeit befasst sich daher mit einem alternativen Ansatz: Der biotechnologischen Produktion von Squalen in marinen Eukaryoten aus der Familie der Thraustochytriden. Thraustochytriden sind einzellige Eukaryoten, die in marinen Habitaten vorkommen und große Mengen an Lipiden produzieren und in ihren Zellen einlagern. Der Anteil an Squalen am Gesamtlipid hängt dabei stark von den gewählten Kultivierungsbedingungen ab. In dieser Arbeit wurde zunächst der Einfluss von sauerstofflimitierenden Bedingungen auf das Wachstum und die Squalenproduktivität des Wildtyps Schizochytrium sp. S31 untersucht. Dafür wurde der Organismus im Schüttelkolben und im Bioreaktor unter der Anwendung verschiedener Prozessführungsstrategien kultiviert. Die respiratorische Aktivität wurde in beiden Kultivierungssystemen durch Analytik der Gaszusammensetzung des Abgases bzw. des Kopfraumes in Echtzeit überwacht. Unter sauerstofflimitierenden Bedingungen erzielte die Fed-Batch-Kultivierung eine Squalenausbeute von 1,1 g/L. Mit dem Ziel, die biotechnologische Produktion von Squalen kostengünstiger und im Sinne einer Kreislaufwirtschaft zu gestalten, beschäftigte sich der zweite Teil dieser Arbeit mit dem Einsatz von potentiellen Nebenströmen als Mediumersatz. Es gelang, die komplexe Stickstoffquelle des Mediums für die Kultivierung von Thraustochytriden durch potentielle Restbiomasse aus der Kultivierung des Basidiomyceten Pleurotus ostreatus zu ersetzen. Durch enzymatische Hydrolyse wurde dafür ein stickstoffreiches Extrakt aus den Pilzbestandteilen, spezie

The cytochrome P450 monooxygenase (CYP) superfamily comprises hemethiolate enzymes that perform remarkable regio- and stereospecific oxidative chemistry. As such, CYPs are key agents for the structural and functional tailoring of triterpenoids, one of the largest classes of plant natural products with widespread applications in pharmaceuticals, food, cosmetics, and agricultural industries. In this review, we provide a full overview of 149 functionally characterised CYPs involved in the biosynthesis of triterpenoids and steroids in primary as well as in specialised metabolism. We describe the phylogenetic distribution of triterpenoid- and steroid-modifying CYPs across the plant CYPome, present a structure-based summary of their reactions, and highlight recent examples of particular interest to the field. Our review therefore provides a comprehensive up-to-date picture of CYPs involved in the biosynthesis of triterpenoids and steroids in plants as a starting point for future research.

The tree of heaven, Ailanthus altissima (MILL.) SWINGLE, is a globally invasive plant known to secrete allelopathic metabolites called quassinoids. Quassinoids are highly modified triterpenoids. So far, nothing has been known about the biochemical basis of quassinoid biosynthesis. Here, based on transcriptome and metabolome data of Ailanthus altissima, we present the first three steps of quassinoid biosynthesis, which are catalysed by an oxidosqualene cyclase and two cytochrome P450 monooxygenases, resulting in the formation of the protolimonoid melianol. Strikingly, these steps are identical to the first steps of the biosynthesis of limonoids, structurally different triterpenoids from sister plant families within the same order Sapindales. Our results are therefore not only important to fully understand the biosynthesis of complex triterpenoids in plants, but also confirm the long-standing hypothesis that quassinoids and limonoids share an evolutionary origin. In addition, our transcriptome data for Ailanthus altissima will be beneficial to other researchers investigating the physiology and ecology of this invasive tree.

A series of N-acyl glucosamine-bearingtriterpenoidsaponins has been synthesized with cytotoxic activities evaluated against HL-60, PC-3, HCT-116, and CT-26 tumor cells. Saponins incorporated anoleanolic acid (OA) triterpenoidal core exhibited the highest cytotoxic activity. To study the influence of the lengths of acyl-carbon chain onN-position of glucosamine, cells were treated with28-propargylamides and then reacted with an azido-fluorogenic probe under CuAACclickreactions to visualize the intact distributions of these compounds by confocal microscopy and flow cytometry; it was found that cytotoxic-active compounds (30–32) located in the cytosol and inactivecompounds bearing longer carbon chains (33–35) were impenetrable across cell membranes.Our study demonstrated the defined lipophilic acyl-carbon chain length can precisely regulate thecytotoxic activityof saponins, which is useful for the future development of cytotoxic agents.Furthermore, using quantitative proteomics and immunolabeling,the mechanism ofcytotoxicity induced by the synthetic saponin after membrane penetration could be a result of activation of death receptor pathway and inhibition of PI3K/Akt/mTOR pathway., QC 20200505

Gotu kola (Centella asiatica) is a traditional herbal plant that has been reported have a variety of pharmacological activities. The compounds of gotu kola that play a role on pharmacological activities are triterpene group compounds, namely madecasosside (MD), asiaticoside (AS), madecassic acid (AM), and asiatic acid (AA). Stress can affect the production of biomass and secondary metabolite compounds in plants. The aims of the study is to analyze the effect of salinity and drought stress on biomass and 4 compounds of triterpene in gotu kola. Harvesting is done when the plant is 8 weeks old. The yield of the biomass was analyzed and then extracted using methanol solvent to be analyzed secondary metabolite levels using the high performance liquid chromatography (HPLC) method.  The lowest crop biomass was obtained at 50% of field capacity and 3,000 ppm salt content. The highest levels of MD and AS were established in conditions of 100% field capacity and 1,000 ppm salt content. The 50 and 100% field capacity and 1,000-3,000 ppm salt content did not affect the levels of AM and AA.

Gotu kola (Centella asiatica) is a traditional herbal plant that has been reported have a variety of pharmacological activities. The compounds of gotu kola that play a role on pharmacological activities are triterpene group compounds, namely madecasosside (MD), asiaticoside (AS), madecassic acid (AM), and asiatic acid (AA). Stress can affect the production of biomass and secondary metabolite compounds in plants. The aims of the study is to analyze the effect of salinity and drought stress on biomass and 4 compounds of triterpene in gotu kola. Harvesting is done when the plant is 8 weeks old. The yield of the biomass was analyzed and then extracted using methanol solvent to be analyzed secondary metabolite levels using the high performance liquid chromatography (HPLC) method.  The lowest crop biomass was obtained at 50% of field capacity and 3,000 ppm salt content. The highest levels of MD and AS were established in conditions of 100% field capacity and 1,000 ppm salt content. The 50 and 100% field capacity and 1,000-3,000 ppm salt content did not affect the levels of AM and AA.

Small lipophilic molecules present in foods of plant origin have relevant biological activities at rather low concentrations. Evidence suggests that phytosterols, carotenoids, terpenoids, and tocopherols can interact with different metabolic pathways, exerting beneficial effects against a number of metabolic diseases. These small molecules can modulate triacylglycerol absorption in the intestine and the biosynthesis of chylomicrons, the lipid carriers in the blood. Once in the bloodstream, they can impact lipoprotein clearance from blood, thereby affecting fatty acid release, incorporation into adipocytes and triglyceride reassembling and deposit. Consequently, some of these molecules can regulate pathophysiological processes associated to obesity and its related conditions, such as insulin resistance, metabolic syndrome and type-2 diabetes. The protective capacity of some lipophilic small molecules on oxidative and chemotoxic stress, can modify the expression of key genes in the adaptive cellular response, such as transcription factors, contributing to prevent the inflammatory status of adipose tissue. These small lipophilic compounds can be incorporated into diet as natural parts of food but they can also be employed to supplement other dietary and pharmacologic products as nutraceuticals, exerting protective effects against the development of metabolic diseases in which inflammation is involved. The aim of this review is to summarize the current knowledge of the influence of dietary lipophilic small biomolecules (phytosterols, carotenoids, tocopherols, and triterpenes) on lipid transport, as well as on the effects they may have on pathophysiological metabolic states, related to obesity, insulin resistance and inflammation, providing an evidence-based summary of their main beneficial effects on human health.

Acanthamoeba genus is a widely distributed and opportunistic parasite with increasing importance worldwide as an emerging pathogen in the past decades. This protozoan has an active trophozoite stage, a cyst stage, and is dormant and very resistant. It can cause Acanthamoeba keratitis, an ocular sight-threatening disease, and granulomatous amoebic encephalitis, a chronic, very fatal brain pathology. In this study, the amoebicidal activity of sixteen Laurencia oxasqualenoid metabolites and semisynthetic derivatives were tested against Acanthamoeba castellanii Neff. The results obtained point out that iubol (3) and dehydrothyrsiferol (1) possess potent activities, with IC values of 5.30 and 12.83 µM, respectively. The hydroxylated congeners thyrsiferol (2) and 22-hydroxydehydrothyrsiferol (4), active in the same value range at IC 13.97 and 17.00 µM, are not toxic against murine macrophages; thus, they are solid candidates for the development of new amoebicidal therapies.

BACKGROUND Olive oil extraction generates a large amount of residue consisting mainly of the pomace and leaves when using a two‐phase centrifugation system. The aim of this study was to assess the content of phenolic and triterpene compounds in the by‐products produced in Spanish olive oil mills. RESULTS Olive pomace had concentrations of phenolic and triterpene substances lower than 2 and 3 g kg−1, respectively. The leaves contained a high concentration of these substances, although those collected from ground‐picked olives had lost most of their phenolic compounds. Moreover, the sediment from the bottom of the olive oil storage tanks did not have a significant amount of these substances. By contrast, a new by‐product called olive pomace skin has been revealed as a very rich source of triterpenic acids, the content of which can reach up to 120 g kg−1 in this waste product, maslinic acid comprising around 70% of total triterpenics. CONCLUSION Among the by‐products generated during extraction of olive oil, olive pomace skin has been discovered to be a very rich source of triterpenic acids, which can reach up to 120 g kg−1 of the waste. These results will contribute to the valorization of olive oil by‐products. © 2017 Society of Chemical Industry

Das Ziel dieser Disssertation war es, bioaktive Naturstoffe zu identifizieren, die mit X-linked Inhibitory of Apoptosis Protein (XIAP), Östrogen Rezeptoren (ER und ER) und Protein-Tyrosin-Phosphatase 1B (PTP1B) interagieren. Dazu wurden drei Pflanzen untersucht: Ephedra sinica, Antidesma ghaesembilla und Agrimonia pilosa. Im Rahmen dieser Arbeit wurde eine Interaktion des Ethanol-Extrakts der oberirdischen Teile von Ephedra sinica mit XIAP entdeckt. Das XIAP-Protein ist das einzige bekannte zelluläre Protein, das die Aktivität der Säugetier-Caspasen inhibiert und so eine Apoptose-Resistenz hervorruft. Bioaktivitätsgeleitete Fraktionierung mittels eines in vitro-Flureszenz-Polarisierungs (FP)-Assays führte zu der Erkenntnis, dass mit Proanthocyanidinen angereicherte Fraktionen eine starke Aktivität besitzen. Der IC50 Wert der aktivsten Fraktion beträgt 9,57 M (CI95: 9,07-10,12 M), das entspricht einer Konzentration von 27,29 g/ mL (CI95: 25,88-28,87 g/ mL). Die Proben wurden mittels Thiolytischem Degradierungs/ HPLC-MS-Assay, LC-HRMS und 1-D-NMR analysiert. Mit Hilfe des Tiolytische Degradierungs/ HPLC-MS-Assays wurde ein mittlerer Polymerisationsgrad von 9,50 0,23 Einheiten für die aktivste Fraktion und 11,42 0,64 für die chemisch ähnlichste inaktive Fraktion. Die chemische Charakterisierung identifizierte (epi)Gallocatechin (76.58 1.00 % aktive; 80.71 2.71 % inaktive Probe) und (epi)Catechin Einheiten als Bausteine der untersuchten Proanthocyanidine. Interessanterweise sind diese Proanthocyanidine eine komplexe Mischung aus doppelt verbundenen A-Typ- (Bindung 2-O-7, 4-6) und einfach verbundenen B-Typ-Einheiten. Die identifizierten oligomeren Proanthocyanindine von E. sinica zeigten eine Inhibition von XIAP in vitro und in zellulären Assays. Der Antidesma ghaesembilla-Baum wurde in der traditionellen Medizin zum Abführen, gegen Kopfschmerzen, als Menstruationsstimulans und zur Steigerung der Milchproduktion verwendet. Dies lässt unter anderem auf eine mögliche Inter, Three plants were investigated in the course of this work: Ephedra sinica, Antidesma ghaesembilla and Agrimonia pilosa. The major aim was to identify bioactive constituents interacting with X-linked inhibitory apoptosis protein (XIAP), estrogen receptors (ER and ER), and protein tyrosine phosphatase 1B (PTP1B). The ethanol extract of the aerial parts of Ephedra sinica has been identified to interact with XIAP, which is the only known cellular protein, that inhibits activity of mammalian caspases and promotes resistance to apoptosis. Bioactivity guided fractionation monitored by an in vitro fluorescence polarization (FP) assay identified proanthocyanidin-enriched fractions as active principles. The most active fraction showed an IC50 value of 9.57 M (CI95: 9.07-10.12 M) corresponding to a concentration of 27.29 g/ mL (CI95: 25.88-28.87 g/ mL). Samples were analysed by a thiolytic degradation/ HPLC-MS assay, LC-HRMS and 1-D-NMR. The thiolytic degradation/ HPLC-MS assay revealed a mean degree of polymerisation of 9.50 0.23 units for the active fraction and 11.42 0.64 units for the most closely related inactive fraction. Chemical characterization identified (epi)gallocatechin (76.58 1.00 % active; 80.71 2.71 % inactive sample) and (epi)catechin units as building blocks. Interestingly, the investigated proanthocyanidins turned out to be a complex mixture of double linked A-type (binding 2-O-7, 4-6) and single linked B-type units. The identified oligomeric proanthocyanidins of Ephedra sinica exhibited XIAP inhibition in vitro and in cellular assays. The tree Antidesma ghaesembilla, also known as black currant tree has been used in traditional medicine as purgative, to treat headache, to stimulate menstrual flow and to increase breast milk production. Part of the described activities is possibly attributable to interactions with estrogenic receptors. Dichloromethane and methanol extracts of the bark of the plant exhibited notable estrogenic but also subtype specific anti-e, submitted by Mag. pharm. Sibylle Schäfer, Zusammenfassung in deutscher Sprache, Abweichender Titel laut Übersetzung der Verfasserin, University of Innsbruck, Dissertation, 2017, OeBB, (VLID)1974064

As a part of the continuing search for bioactive compounds with the Madagascar International Cooperative Biodiversity Group (ICBG), and in collaboration with the Natural Products Discovery Institute of the Institute for Hepatitis and Virus Research (IHVR), thirteen plant extracts were investigated for antiplasmodial activity, thirteen plant extracts were investigated for antiproliferative activity, and one extract was investigated for inhibitors of the shikimate pathway in Plasmodium falciparum. Bioassay-guided fractionation of the extracts led to the identification of nineteen compounds with both antiplasmodial and antiproliferative activity, and thirteen compounds with only antiproliferative activity. Thirteen of these compounds (2.1 – 2.9, 3.3, 3.4, 4.5, and 5.1) were previously unknown. In addition total synthesis was used to confirm the structure of one new compound (4.5) and two other new natural-product like compounds (4.6 and 4.7) were also synthesized and investigated for antiplasmodial activity.

As a part of the continuing search for bioactive compounds with the Madagascar International Cooperative Biodiversity Group (ICBG), and in collaboration with the Natural Products Discovery Institute of the Institute for Hepatitis and Virus Research (IHVR), thirteen plant extracts were investigated for antiplasmodial activity, thirteen plant extracts were investigated for antiproliferative activity, and one extract was investigated for inhibitors of the shikimate pathway in Plasmodium falciparum. Bioassay-guided fractionation of the extracts led to the identification of nineteen compounds with both antiplasmodial and antiproliferative activity, and thirteen compounds with only antiproliferative activity. Thirteen of these compounds (2.1 – 2.9, 3.3, 3.4, 4.5, and 5.1) were previously unknown. In addition total synthesis was used to confirm the structure of one new compound (4.5) and two other new natural-product like compounds (4.6 and 4.7) were also synthesized and investigated for antiplasmodial activity.

BACKGROUND: Olive leaves and fruit possess bioactive substances such as phenolic compounds and triterpenic acids that can be obtained from olive by-products generated during olive oil extraction. The aim of the present study was the characterization and quantification of these compounds in Picual and Arbequina cultivars from different locations and throughout two seasons in both olive leaves and fruit. RESULTS: The major phenolic compound identified in the leaves was oleuropein, and the total content of phenolic compounds in this material reached 70 g kg fresh weight. The leaves were also rich in triterpenic acids (20 g kg fresh weight), with oleanolic acid being the most concentrated among them. With regard to olives, oleuropein and demethyloleuropein were the main phenolic compounds in the pulp of Picual and Arbequina cultivars, and the total concentration of these phenolic compounds reached 3.5% fresh weight. Olives can also be an important source of triterpenic acids, although this is mainly the skin part, where the maslinic and oleanolic acids are concentrated. CONCLUSION: Olive leaves can contain up to 70 g kg phenolic compounds and 20 g kg triterpenic acids, and olive fruit can contain up to 35 g kg of the former and 3 g kg of the latter. It must also be noted that this level was constant both between seasons and orchard locations. © 2016 Society of Chemical Industry.

Russeting, a major concern for the apple production sector, is due to the accumulation of suberin in the inner part of the cell wall of the epidermal cell layer. Since the 60s, many studies have been performed to better understand the tight relationship occurring between the cuticle development and the suberization process. However, the genetic factors which drive the russeting process, as well as the metabolic genes which are involved in the suberization process, remain unclear. The first aim of this thesis was to identify the different genetic actors of the russeting process. For this, a transcriptomic approach comparing waxy and russeted tissues was used to investigate the different pathways which are involved in this particular trait. Among the identified genes, a large number involved in the cuticle biosynthesis had their expression repressed in the russeted skin. Conversely, genes likely involved in the suberization process were identified and displayed an enhanced expression in these tissues. A lipid surface analysis of the russeted and waxy apple skins in a semi-russeted apple confirmed these results. Interestingly, cell wall modification genes seemed to be also involved in this russeting program. In a second step, candidate transcription factor genes, which might be involved in the regulation of russeting, were investigated. Among these, MdMYB93, which is able to trigger the expression of a large part of the genes identified in our transcriptomic studies, is now considered as a master regulator of suberin biosynthesis in apple. Altogether the present thesis provides answers which help to better understand the mechanisms leading to russeting. It also opens new insights for further work aiming at unravelling the remaining unexplored processes involved in apple russeting and, more generally, in the plant suberization process., (AGRO - Sciences agronomiques et ingénierie biologique) -- UCL, 2016

Saponins are a group of structurally diverse steroid and triterpenoid glycosides that can naturally be found in plants as secondary metabolites. Many biological effects have been ascribed to saponins and their sapogenin, the unglycosylated steroid or triterpenoid. Many of the effects are pharmacological including antineoplastic, anti-inflammatory, antidiabetic and several other effects. Saponins also have diverse ecological effects making them relevant for plant defenses including antibacterial, antifungal, antiprotozoal, antiviral, and herbivore-poisoning effects. Hederagenin and oleanolic acid are two of the most abundant triterpene sapogenins and co-occur in multiple plants. Each sapogenin by itself has a wide range of ecological effects. The various saponins based on hederagenin and oleanolic acid extend that range even further. This report reviews the extensive ecological effects of hederagenin, oleanolic acid and their saponins to highlight both their antimicrobial potential and their ecological role as plant defense compounds. To further elucidate the role of hederagenin- and oleanolic acid saponins as plant defense compounds against herbivores a line of experiments with the saponin containing winter cress Barbarea vulgaris ssp. arcuata were conducted. B. vulgaris contains both hederagenin- and oleanolic acid saponins and is the only plant species in the family of Brassicaceae in which saponins have been confirmed. Two subtypes of B. vulgaris ssp. arcuata, were challenged with herbivory to analyze changes in the plant-internal saponin content. The two chemically divergent subtypes, P and G, differ in their susceptibility towards certain herbivores and pathogens. This is partly attributed to their different saponin profiles. Four herbivores from different feeding guilds were used to induce saponin accumulation in B. vulgaris, including larvae of two lepidopteran species, Spodoptera littoralis and Plutella xylostella, the aphid Aulacorthum solani and a roun

Saponins are a group of structurally diverse steroid and triterpenoid glycosides that can naturally be found in plants as secondary metabolites. Many biological effects have been ascribed to saponins and their sapogenin, the unglycosylated steroid or triterpenoid. Many of the effects are pharmacological including antineoplastic, anti-inflammatory, antidiabetic and several other effects. Saponins also have diverse ecological effects making them relevant for plant defenses including antibacterial, antifungal, antiprotozoal, antiviral, and herbivore-poisoning effects. Hederagenin and oleanolic acid are two of the most abundant triterpene sapogenins and co-occur in multiple plants. Each sapogenin by itself has a wide range of ecological effects. The various saponins based on hederagenin and oleanolic acid extend that range even further. This report reviews the extensive ecological effects of hederagenin, oleanolic acid and their saponins to highlight both their antimicrobial potential and their ecological role as plant defense compounds. To further elucidate the role of hederagenin- and oleanolic acid saponins as plant defense compounds against herbivores a line of experiments with the saponin containing winter cress Barbarea vulgaris ssp. arcuata were conducted. B. vulgaris contains both hederagenin- and oleanolic acid saponins and is the only plant species in the family of Brassicaceae in which saponins have been confirmed. Two subtypes of B. vulgaris ssp. arcuata, were challenged with herbivory to analyze changes in the plant-internal saponin content. The two chemically divergent subtypes, P and G, differ in their susceptibility towards certain herbivores and pathogens. This is partly attributed to their different saponin profiles. Four herbivores from different feeding guilds were used to induce saponin accumulation in B. vulgaris, including larvae of two lepidopteran species, Spodoptera littoralis and Plutella xylostella, the aphid Aulacorthum solani and a roun

Two new triterpenes (1 and 2) and two new triterpene glycosides (3 and 4), along with six known triterpenes (5-10) were isolated from the leaves of Ilex latifolia. The structures of new compounds were elucidated on the basis of NMR, HR-MS, and X-ray diffraction analysis. Compounds 4 and 5 showed potent inhibitory activity on oleic acid/palmitic acid induced triglyceride accumulation on HepG2 cells. (C) 2015 Elsevier B.V. All rights reserved.

Two new triterpenes (1 and 2) and two new triterpene glycosides (3 and 4), along with six known triterpenes (5-10) were isolated from the leaves of Ilex latifolia. The structures of new compounds were elucidated on the basis of NMR, HR-MS, and X-ray diffraction analysis. Compounds 4 and 5 showed potent inhibitory activity on oleic acid/palmitic acid induced triglyceride accumulation on HepG2 cells. (C) 2015 Elsevier B.V. All rights reserved.

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.

Two new triterpenes (1 and 2) and two new triterpene glycosides (3 and 4), along with six known triterpenes (5-10) were isolated from the leaves of Ilex latifolia. The structures of new compounds were elucidated on the basis of NMR, HR-MS, and X-ray diffraction analysis. Compounds 4 and 5 showed potent inhibitory activity on oleic acid/palmitic acid induced triglyceride accumulation on HepG2 cells. (C) 2015 Elsevier B.V. All rights reserved.

Cucurbitacins constitute a group of high-value triterpenes with various pharmacological and ecological effects. Despite their strong activities, availability is low due to a scarce natural production level. This project was done in collaboration with the EU-funded TriForC project that focuses on discovery, production and commercial utilization of high-value plant triterpenes. Therefore, the enhancement of natural cucurbitacin production was studied with a goal of sustainable production and commercialization. Cucurbitacins are derived from the sterol biosynthetic pathway in which 2,3-oxidosqualene is the last common precursor between sterol and cucurbitacin formation. 2,3-oxidosqualene is further derived from the oxygenation of squalene catalyzed by the squalene epoxidase. In the cucurbitacin biosynthetic pathway 2,3-oxidosqualene is cyclized by the cucurbitadienol synthase producing cucurbitadienol, which marks the first catalytic step in cucurbitacin biosynthesis. Cucurbitadienol can then be further elaborated by different enzymes resulting in different cucurbitacins. This study investigated the enhancement of cucurbitacin production using Cucurbita pepo spp pepo as a model system. This was attempted with by treating 10-day old seedlings with methyl-jasmonate. Furthermore, four squalene epoxidase genes CpSQE1, CpSQE1.2, CpSQE2 and CpSQE3 were identified. The link between the flux of precursor 2,3-oxidosqualene and cucurbitacin was then investigated by expression analysis using quantitative real-time PCR and by transient expression in Nicotiana benthamiana. CpSQE1 was found to have tissue-specific expression mainly in leaves and cotyledon tissues. Furthermore, increased expression of CpSQE1 was not associated by elevated levels of cucurbitacin accumulation in cotyledon and root tissues. Based on the expression analysis, transient expression in N. benthamiana and the clustering in a phylogenetic tree, CpSQE1 was suggested to be primarily involved in pri

Cucurbitacins constitute a group of high-value triterpenes with various pharmacological and ecological effects. Despite their strong activities, availability is low due to a scarce natural production level. This project was done in collaboration with the EU-funded TriForC project that focuses on discovery, production and commercial utilization of high-value plant triterpenes. Therefore, the enhancement of natural cucurbitacin production was studied with a goal of sustainable production and commercialization. Cucurbitacins are derived from the sterol biosynthetic pathway in which 2,3-oxidosqualene is the last common precursor between sterol and cucurbitacin formation. 2,3-oxidosqualene is further derived from the oxygenation of squalene catalyzed by the squalene epoxidase. In the cucurbitacin biosynthetic pathway 2,3-oxidosqualene is cyclized by the cucurbitadienol synthase producing cucurbitadienol, which marks the first catalytic step in cucurbitacin biosynthesis. Cucurbitadienol can then be further elaborated by different enzymes resulting in different cucurbitacins. This study investigated the enhancement of cucurbitacin production using Cucurbita pepo spp pepo as a model system. This was attempted with by treating 10-day old seedlings with methyl-jasmonate. Furthermore, four squalene epoxidase genes CpSQE1, CpSQE1.2, CpSQE2 and CpSQE3 were identified. The link between the flux of precursor 2,3-oxidosqualene and cucurbitacin was then investigated by expression analysis using quantitative real-time PCR and by transient expression in Nicotiana benthamiana. CpSQE1 was found to have tissue-specific expression mainly in leaves and cotyledon tissues. Furthermore, increased expression of CpSQE1 was not associated by elevated levels of cucurbitacin accumulation in cotyledon and root tissues. Based on the expression analysis, transient expression in N. benthamiana and the clustering in a phylogenetic tree, CpSQE1 was suggested to be primarily involved in pri

Two novel squalene-derived triterpenes, spirodehydrovenustatriol (3) and 14-keto-dehydrothyrsiferol (4) were isolated from the red alga Laurencia viridis, together with two new and unusual C17 terpenoids, adejen A (5) and B (6). These truncated structures possess structural similarities with other known squalene metabolites and their biogenetic origin has been proposed on the basis of an oxidative process of the squalene skeleton. All the structures were elucidated by extensive use of 2D NMR spectroscopic methods.

L'industrie forestière produit beaucoup de rebuts souvent peu utilisés tels que les écorces. D'ailleurs, on estime que 3,5 millions de tonnes d'écorces anhydres ont été produites au Québec en 2002. La nette majorité de ces écorces n'est pas valorisée et est incinérée pour la production énergétique. Actuellement, il existe peu de techniques au Québec autres que l'enfouissement et le brûlage pour disposer des résidus de l'industrie du bois de sciage. Ces déchets polluants et non valorisés par ces industries seraient donc une source très intéressante de produits finis. En effet, une vaste gamme de produits naturels présents au sein du règne végétal sont connus depuis fort longtemps pour avoir des propriétés thérapeutiques et pharmacologiques. Certains triterpènes de la famille du lupane, présents dans les écorces externes du bouleau blanc {Betula papyrifera), sont des molécules naturelles connues depuis longtemps pour diverses activités biologiques intéressantes. Entre autres, le bétulinol et l'acide bétulinique sont réputés pour plusieurs actions antitumorales notables. Ces composés sont d'un grand intérêt dans le traitement des maladies cancéreuses compte tenue du coût élevé de production des médicaments de synthèse et de la résistance croissante des lignées cellulaires cancéreuses face aux traitements existants. À cela s'ajoute une très grande acessibilité de la matière première. Ainsi, le développement de nouveaux agents bioactifs d'origine naturel, dotés de mécanismes d'actions différents est pourvu d'un avenir très prometteur. Cependant, la faible hydrosolubilité des triterpènes du lupane est un facteur nuisible aux propriétés pharmacologiques et à un développement au-delà des études in vitro. L'accroissement de l'hydrosolubilité et des propriétés pharmacologiques de triterpènes hydrophobes représente donc les objectifs de cette recherche doctorale. Pour ce faire, l'incorporation d'unités polaires et biocompatibles, ainsi que la modification même du squelette tri

Les triterpènes pentacycliques de type lupane (lupéol, bétulinol et acide bétulinique) font l'objet de plusieurs études concernant leurs propriétés médicinales variées. L'acide bétulinique, molécule la plus étudiée de cette série, possède une activité anticancéreuse in vitro sur un large éventail de tumeurs. Cette action chimiothérapeutique a également été démontrée sur un modèle de souris porteuses de tumeurs murines. Contrairement aux agents anti-tumoraux connus, l'acide bétulinique est peu toxique et possède une sélectivité vis-à-vis des mélanomes. Toutefois, sa faible hydrosolubilité est un obstacle majeur pour le développement des études de phase préclinique. Pour améliorer l'hydrosolubilité de l'acide bétulinique et de ses dérivés, une série de glycosides triterpéniques ont été synthétisés. Leur solubilité relative dans divers solvants a été déterminée et leur activité cytotoxique a été évaluée in vitro sur cellules cancéreuses. La fonction anomérique des sucres benzoylés D-glucose, L-rhamnose et Darabinose a été déprotégée préférentiellement et activée par les trichloroacétimidates (59-69%). Ensuite, les réactions de glycosidation et de déprotection subséquentes ont permis l'obtention de 15 monodesmosides triterpéniques (52-90%, 2 étapes; 41-50%, 3 étapes) dont certains n'ont jamais été répertoriés dans la littérature. Le bétulinol a exercé la plus forte activité anticancéreuse des triterpènes testés (IC50 = 4,5-10,3 uM), mais l'ajout d'une section D-glucose en position 3 ou 28 a entraîné une perte totale d'activité. En revanche, la (3-D-glucosidation du lupéol (IC50 >100 uM) a bonifié significativement l'activité cytotoxique (IC50 = 14-15,0 uM). Par ailleurs, les (3-Dglucoside et a-D-arabinoside de bétulinate de méthyle ont montré une forte activité anticancéreuse dépassant celle de la molécule initiale (IC50 = 3,93-8,4 uM et 13,3-18 uM respectivement). La glycosidation de l'acide bétulinique a entraîné des gains au niveau de la cytotoxicité et de la sélecti

L'acide bétulinique 1, un triterpène au squelette de lupane, est connu pour ses activités thérapeutiques. Entre autres, ce composé possède une activité anticancéreuse et antivirale. L'acide bétulinique 1 s'est avéré cytotoxique contre de nombreuses lignées de cellules cancéreuses. De plus, il présente une faible toxicité pour les cellules saines de l'organisme ce qui en fait un traitement potentiel pour certaines tumeurs cancéreuses. Cependant, l'acide bétulinique 1 présente une limite d'application étant donné sa faible biodisponibilité dans l'organisme. La faible biodisponibilité du composé est possiblement due à sa faible hydrophilicité. Ce projet vise la synthèse d'un analogue glycosidique de l'acide bétulinique 1^ pour en augmenter l'hydrosolubilité dans le but d'améliorer la biodisponibilité du composé dans l'organisme tout en conservant une activité anticancéreuse. Pour ce faire, une section polaire et hydrophile, le glucose 4, est ajoutée à la fonction alcool du composé. L'objectif principal du projet de recherche est l'élaboration de la synthèse d'un dérivé glycosidique bioactif de l'acide bétulinique 1 pour en augmenter l'hydrosolubilité. La formation de l'acide 3-Op-D-glucopyranosylbétulinique 15 a été réalisée en cinq étapes en utilisant l'activation par les trihalogénoacétimidates. Le couplage de l'acide bétulinique 1 et du l-trichloroacétimidates-2,3,4,6-tétra-O-benzoyl-glucopyranose 7b a été effectuée à l'aide du catalyseur triméthylsilyl trifluorométhanesulfonate (TMSOTf). La synthèse a été réalisée avec un rendement de 32 %. Le coefficient de partage de l'acide 3-0-(3-D-glucopyranosylbétulmique 15 a été évalué et montre que l'hydrophilicité de ce dernier est beaucoup plus importante que celle du composé de départ, l'acide bétulinique 1, ce qui pourrait permettre d'améliorer sa biodisponibilité in vivo. L'ajout d'une section sucre à l'acide bétulinique 1 peut avoir une influence sur l'activité anticancéreuse de la molécule. L'activité anticancéreuse

Column chromatography of the acetone extract of the lichen Stereocaulon azoreumafforded several substances identified by chemical and spectral means: a-amyrin, lupeol, tarazerol, ursolic acid, ergosterol peroxide, brassicasterol, cerevisterol, stietic acid and accione condesation derivative, lobaric acid.