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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
111

Effects of cationic antimicrobial peptides on Candida and Saccharomyces species

Harris, Mark R. January 2010 (has links)
Antimicrobial peptides (AMPs) are found throughout the animal kingdom and act as a natural defence against a broad spectrum of pathogens. These peptides are toxic to invading organisms without acting on host cells, so are of interest for their potential to act as potent new drugs against pathogenic organisms. AMPs traverse the cell wall and predominantly target the plasma membrane, resulting in destabilisation, leakage of intracellular components and cell death. In this thesis the mode of action of several AMPs was investigated. The role of the cell wall was studied and found to mediate peptide binding, the inhibition of certain cell wall components also increased peptide action, subsequent internalisation events were observed with varying localisation patterns and the effect of several genes that alter cell susceptibility to AMP were examined. Several Candida albicans mutants, each deficient in cell wall protein mannosylation, were tested in relation to their susceptibility to AMPs. It was discovered that cells lacking or deficient in the phosphomannan fraction, with a concomitant reduction in surface negative charge, correlated with reduced susceptibility to AMP action. To ascertain whether peptide binds to negatively charged phosphate, the effect of exogenous glucosamine 6-phosphate (but not glucosamine hydrochloride) was studied demonstrating that peptide efficacy was reduced due to the presence of exogenous phosphate. More specifically, sequestration of the truncated cationic AMP dermaseptin S3 (DsS3(1-16)) was reduced in these phosphomannan deficient mutants. Microscopy analysis of fluorescein tagged DsS3(1-16) also revealed the differential localisation patterns of this AMP: transiently binding to the plasma membrane, localisation to the vacuole or diffuse distribution throughout the cytoplasm. It is proposed that for these cationic AMPs to exert their full antifungal action they must first bind to the negatively charged phosphate. The echinocandins are a relatively new class of antifungal that function by inhibiting 1,3-β glucan synthase resulting in reduced 1,3-β glucan in the cell wall. As AMPs have to traverse the cell wall it was postulated that cells lacking this fraction would display increased AMP binding to the membrane. Clinical isolate strains of Candida and Cryptococcus spp. were acquired to test their susceptibility to AMP and echinocandin combinations. Comparing the fractional inhibitory concentration index (FICI) (supported by viable cell counts and on a solid surface using disc diffusion assays) synergy was observed between caspofungin, anidulafungin and several AMPs in vitro. In vitro toxicity assays revealed no increase in haemolytic or cytotoxic action on combination. These synergistic combinations could provide a novel treatment against fungal pathogens. The final area of study was based upon work that identified genes whose expression altered cell susceptibility to AMPs. Three genes were selected for investigation that upon deletion increased the action of DsS3(1-16) or magainin 2 on S. cerevisiae. Results from growth analysis, peptide sequestration and cell viability counts confirmed that deletion of HAL5, LDB7 or IMP2’ did increase susceptibility. Additionally, deletion of HAL5 increased the probability of cell depolarisation upon peptide exposure. Expression of GFP-tagged Imp2’ also increased when cells were exposed to DsS3(1-16). It was concluded that deletion of HAL5 increases depolarisation due to insufficient potassium efflux, leading to ion leakage and cell death facilitated by AMP action. Double strand break repair and DNA protection are probably compromised upon deletion of LDB7 and IMP2’, increasing the inhibitory action of DsS3(1-16) that has previously been shown to bind to DNA.
112

Determination of the antibacterial, antioxidant activity, isolation and characterisation of active compounds from the leaves of Rhys Leptodictia plant

Matamela, Tshifhiwa 02 1900 (has links)
M Tech. (Chemistry, Faculty of Applied and Computer Sciences), Vaal University of Technology. / Rhus leptodictya commonly known as a mountain karee belongs to the family Anacadeceae and has been used since antiquity in tradition medicine. In the present study antimicrobial and antioxidant potentials of the leaves of Rhus leptodictya were studied, followed by isolation of at least one active compound which showed antibacterial and antioxidant potentials. Extractions were performed based on the polarity of the solvent used. The solvents used were hexane, dichloromethane, ethyl acetate, acetone and methanol. Dichloromethane was found to be extracting more compounds than the other used solvents. Thin layer chromatography (TLC) was used to determine the chemical composition of the extracts by employing different solvent systems. The results showed that, of the solvent systems used, namely ethyl acetate: methanol: water (EMW) 40: 5: 1; chloroform: ethyl acetate: formic acid (CEF) 5: 4: 1 and benzene: ethanol: ammonium hydroxide (BEA) 90:10:1, BEA produced better separations. To determine the antioxidant potential of the leaves, 2.2-diphenyl picrylhydrazyl (DPPH) was used. Different spot with different Rf values were found to be active by show of yellow colour on the TLC plate. The yellow colour is due to the proton gained by DPPH when it reacts with active compound. Bioutography results showed that different leaves were active against selected bacterium. Minimum inhibitory concentration studies showed that the methanol extract was more active against B.subtilis and S.pnuemonia at concentration less than 0.1 mg/ml respectively. Dichloromethane extract was found to be the least effective on S.pneumonia, as compared to the methanol, acetone and ethyl acetate extracts. In terms of the total activity, the ethyl acetate concentration showed better total activity than the other extracts studied in this research. A new compound 7, 8-trihydroxy-2-(4’hydroxy phenyl)-3-5-[5’’, 6’’-dihydroxy-2’’-O-(4’’’hydroxyphenyl)-4-1t-chromen-4’’-one]-41t-chromen-4-one was isolated and characterized by H1-NMR, C13-NMR, MS and IR. According to the literature search, this compound has never been isolated from any plant and it has showed both antioxidant and antibacterial activity.
113

Études phytochimiques de plantes médicinales djiboutiennes à effets antimicrobiens et anticancéreux / Phytochemical study of medicinal plant from Djibouti with antimicrobial and anticancer effects

Elmi Fourreh, Abdirahman 30 November 2018 (has links)
Ce travail a porté sur la bio-analyse de plantes médicinales Djiboutiennes. Ces dernières ont été sélectionnées sur des critères ethnobotaniques appliqués sur les plantes utilisées traditionnellement contre les infections microbiennes. Cette sélection a retenu six plantes qui ont ensuite subi un screening antibactérien et anti oxydant. Les résultats de ce screening ont conduit à étudier trois plantes: Acacia seyal, Indigofera caerulea et Cymbopogon commutatus. La recherche des composés de l’Acacia seyal est effectuée au moyen d’un bio-guidage. Deux extraits, aqueux et méthanolique, de l’écorce de cette plante sont évalués pour leur activité antibactérienne. Quatre composés sont isolés et caractérisés (épicatéchine, catéchine, catéchine digallique et β-sitostérol) et testés pour leurs activités. Par ailleurs quatre extraits (hexanique, acétonique, méthanolique et aqueux) du fruit d’Indigofera caerulea ont été testés pour leurs activités antibactérienne et anti oxydante. Les extraits hexanique et méthanolique sont les plus actifs. Six composés sont isolés de ces extraits (méthyl gallate, acide gallique, rutine, isoquercétine, kaempférol-3- rutinoside et β-sitostérol). Le méthyl gallate inhibe staphylococcus aureus avec une CMI de 64 µg/ mL. Enfin l’activité de l’huile essentielle de Cymbopogon commutatus est testée sur sept souches bactériennes, deux souches fongiques et onze types de cellules cancéreuses. Sur ces dernières, elle présente une forte cytotoxicité avec des IC50 allant de 0,05 µg/mL sur PC3 et HCT116 (cellules cancéreuses de la prostate et colorectales) et à 0,67 µg/mL sur NCI-N87 (cellule cancéreuse gastrique). De façon surprenante, une activité antibactérienne moyenne est observée. L’analyse GCMS de la partie solubilisée dans le milieu de culture a montré que seuls les composés hydrophiles étaient présents. La formulation d’une micro émulsion a été mise au point et les IC50 ont diminué jusqu’à une centaine de fois. Nous avons montré que cette huile essentielle renferme plus de 73,9 % de pipéritone (monoterpène). En conclusion, ces trois plantes ont montré des activités antimicrobiennes, et les travaux confirment leurs utilisations traditionnelles. En plus, nous avons montré qu’elles possèdent d’autres activités biologiques (anti oxydante et anti cancéreuse). Ces résultats devront contribuer à la mise en place d’une pharmacopée traditionnelle et à des formulations de ‘médicaments traditionnels améliorés’ (MTA) / This research focused on the bio-analysis of Djiboutian medicinal plants. These latter were selected on ethnobotanical criteria applied to the plants traditionally used against microbial infections. This selection retained six plants which were then subjected to a biological screening including antibacterial and anti-oxidant activities. Three plants were finally study: Acacia seyal, Indigofera caerulea and Cymbopogon commutatus. The search of compound in Acacia seyal was carried out by means of bio-guidance. Two extracts, aqueous and methanolic, of the bark of this plant were evaluated for their antibacterial activity. Four compounds were isolated, characterized (epicatechin, catechin, digallic catechin and β-sitosterol) and tested for their activity. Also four extracts (hexanic, acetonic, methanolic and aqueous) of the fruit of Indigofera caerulea were tested for their antibacterial and antioxidant activities. The Hexanic and methanolic extracts were the most active. Six compounds were isolated from these extracts (methyl gallate, gallic acid, rutin, isoquercetin, kaempferol-3-rutinoside and β-sitosterol). Methyl gallate inhibited Staphylococcus aureus with a MIC of 64 μg / mL. Finally, the activity of the essential oil of Cymbopogon commutatus was evaluated on seven bacterial strains, two fungal strains and eleven types of cancer cells. On the latter, it exhibits a high cytotoxicity with IC50s ranging from 0.05 μg / mL on PC3 and HCT116 (prostate and colorectal cancer cells) to 0.67 μg/mL on NCI-N87 (gastric cancer cell). Surprisingly, an antibacterial activity not so high was observed. GCMS analysis of the solubilized part in the culture medium showed that only the hydrophilic compounds were present. The formulation of a microemulsion was performed and the IC50 decreased to a hundred times. We have found that this essential oil contained more than 73.9 % piperitone (monoterpene). In conclusion, these three plants showed antimicrobial activities and the work confirms their traditional uses. In addition, we have shown that they have other biological activities (anti-oxidant and anti-cancer). These results should contribute to the establishment of a traditional pharmacopoeia and formulations of 'improved traditional medicines' (MTAs)
114

Antimicrobial activity of some medicinal plant extracts against bacteria causing diarrhoea

Komolafe, Naomi Tope 12 1900 (has links)
Infectious diarrhoea is the second largest single cause of mortality in children under the age of five globally. Bacteria are responsible for most diarrhoeal episodes especially in developing countries, and progressive increase in antimicrobial resistance has given rise to the need to investigate other sources of therapy such as medicinal plants. Ten plant extracts were analysed for their antimicrobial activities using the agar well diffusion and broth microdilution method. Their phytochemical contents were screened, and their effect on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) was used to assess their antioxidant activities. Their toxicity profiles were evaluated using the XTT Cytotoxicity Assay. Water and methanol extracts of Adansonia digitata v ABSTRACT Infectious diarrhoea is the second largest single cause of mortality in children under the age of five globally. Bacteria are responsible for most diarrhoeal episodes especially in developing countries, and progressive increase in antimicrobial resistance has given rise to the need to investigate other sources of therapy such as medicinal plants. Ten plant extracts were analysed for their antimicrobial activities using the agar well diffusion and broth microdilution method. Their phytochemical contents were screened, and their effect on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) was used to assess their antioxidant activities. Their toxicity profiles were evaluated using the XTT Cytotoxicity Assay. Water and methanol extracts of Adansonia digitata seeds and pulp showed no inhibition against all the test organisms, while water and methanol extracts of A. digitata leaves showed inhibition, with minimum inhibitory concentration (MIC) ranging from 0.39 to 6.25mg/ml. Water and methanol extracts of Garcinia livingstonei and Sclerocarya birrea barks showed good activity against all the test organisms, with MICs between 0.39 and 1.56 mg/ml. Alkaloids, phenols, flavonoids, saponins, tannins, and terpenoids were found in one or more of the plant extracts, and all the plant extracts demonstrated scavenging power against DPPH.The cytotoxicity of extracts of Garcinia livingstonei, and Sclerocarya birrea barks ranged between 105.9 μg/ml and 769.9 μg/ml. The results obtained in this study validate the traditional use of A. digitata leaves, G. livingstonei and S. birrea bark in treating bacteria causing diarrhoea. / Life Sciences / M. Sc. (Life Sciences)
115

Les sécoiridoïdes d’Olea europaea et du Lonicera tatarica : matières premières destinées à la conception de nouveaux synthons chiraux pour la synthèse de composés biologiquement actifs et outils pour le développement de nouvelles méthodes d’extraction et de synthèse / Secoiridoids from Olea europaeae and Lonicera tatarica as chiral synthon for bioactive compounds synthesis and as a tool for new extraction and synthetic methodologies development

Lemoine, Hugues 30 November 2012 (has links)
Les sécoiridoïdes sont des monoterpènes hautement fonctionnalisés utilisés comme matières premières chirales renouvelables en hémisynthèse, lorsqu’ils sont abondants au sein des végétaux. Un nouveau procédé vert d’extraction aqueuse et de purification utilisant des résines et la chromatographie de partage centrifuge a permis l’isolement de plus de 100 g d’oleuropéine des feuilles d’Olea europaea et d’une douzaine de grammes de sécologanoside et de sweroside des feuilles de Lonicera tatarica. L’ouverture de la lactone du perpivaloylsweroside a été effectuée en milieu organique apolaire par le TMSONa. Cette réaction a été étendue à 8 lactones commerciales et 5 lactones de sécoiridoïdes. Une approche mécanistique de cette nouvelle réaction a été établie sur la γ-butyrolactone à l’aide d’une étude cinétique. Cette réaction a été utilisée pour la conversion du sweroside en sécologanoside en quatre étapes. Cette approche séquentielle a été appliquée avec succès sur les dérivés du sweroside. Quatre nouveaux analogues du sécologanoside et 9 synthons chiraux originaux ont ainsi été isolés. De plus l’étude de la réactivité de l’oleuropéine a permis l’obtention de 4 nouveaux synthons et un analogue isomérique du sécologanoside. Ces analogues de sécologanoside sont précurseurs de nouveaux alcaloïdes indolo-monoterpèniques. Enfin la double liaison exocyclique du sweroside a pu être sélectivement ozonolysée et épimérisée pour conduire à la formation d’un synthon clé pour la synthèse de diterpènes cytotoxiques marins de types xénicanes. / Secoiridoids are highly functionalized monoterpenes and can be used as renewable raw materials in semi-synthesis when they are abundant in plants. A new green process of water extraction and purification by resins or centrifugal partition chromatography allowed the isolation of more than 100 g of oleuropein from Olea europaea leaves and a dozen of grams of secologanin and sweroside from Lonicera tatarica leaves.The lactone ring opening of perpivaloylsweroside was achieved in apolar solvents by TMSONa. The scope of this reaction was extended to 8 commercial lactones and 5 secoiridoid lactones. A mechanistic approach of this new reaction on γ-butyrolactone was established by kinetic studies. This reaction was used for the conversion of perpivaloylsweroside into secologanin, in four steps. This approach was successfully applied on sweroside derivatives. Four enantiopure secologanin analogs and 9 chiral synthons were isolated. Furthermore the reactivity study of oleuropein afforded 3 new synthons and one isomeric analog of secologanin. These secologanin analogs are synthetic precursors of new indolo-monoterpenic alkaloids. Finally the exocyclic double bond of sweroside was selectively ozonolyzed and epimerized to yield a key synthon for the synthesis of cytotoxic marine diterpenes xenicans.
116

Bioactivity and chromatographic profiles of the selected medicinal plants against candida albicans

Mulaudzi, Takalani Millicent 17 July 2015 (has links)
MSc (Botany) / Department of Botany
117

Traditional health practitioners' practices and the sustainability of extinction-prone traditional medicinal plants

Magoro, Madimetja David 06 1900 (has links)
For centuries Traditional Health Practitioners (THPs) used their indigenous knowledge (IK) in conserving medicinal plants and environments to maintain sustainability. With the rapid environmental, social, economic and political changes occurring in many areas inhabited by rural people exist the danger that the loss of biodiversity from habitat destruction and unsustainable harvesting practices will result in some species becoming extinct. The main aim of the study was to determine the natural habitat of extinction-prone traditional medicinal plants combining the insight of THPs with an ultimate goal of guiding research for the conservation, propagation and cultivation of traditional medicinal plants. Despite problems, opportunities and challenges expressed and identified by THPs, the analysis of data from interview schedule and personal observations, show that the THPs' practices are shaped by historical processes and local cultural values, social norms and their management strategies that are influenced by a broad range of factors. / Agriculture, Animal Health & Human Ecology / M.A. (Human Ecology)
118

Antibacterial free fatty acids from the marine diatom, Phaeodactylum tricornutum

Desbois, Andrew P. January 2008 (has links)
The aim of this thesis was to isolate the compounds responsible for the antibacterial activity of cell extracts of the marine diatom, Phaeodactylum tricornutum. Marine microalgae are not only important primary producers but, due to their phylogenetic diversity, they are also a potential source of novel bioactive compounds. The marine diatom, P. tricornutum, was selected for study because its cell extracts are known to be antibacterial but the compounds responsible have not been isolated. In this thesis, the compounds responsible for the antibacterial activity are isolated from aqueous methanol P. tricornutum cell extracts by column chromatography and reverse phase high-performance liquid chromatography using a bioassay-guided approach. The compounds in three active fractions were identified by mass spectrometry and nuclear magnetic resonance spectroscopy as the unsaturated fatty acids (5Z, 8Z, 11Z, 14Z, 17Z)-eicosapentaenoic acid, (9Z)-hexadecenoic acid and (6Z, 9Z, 12Z)-hexadecatrienoic acid. The fatty acids were found to be antibacterial against Staphylococcus aureus at micromolar concentrations. P. tricornutum exists in different cell morphs and, interestingly, extracts prepared from cultures in the fusiform morph were found to have greater antibacterial activity than extracts from oval cultures. This is explained by greater levels of the three antibacterial fatty acids in the fusiform cell extracts. The antibacterial fatty acids are proposed to be released by enzyme action when the diatom cells lose their integrity. The release of free fatty acids by diatoms is suggested to be a simple, very low cost population-level activated defence mechanism against potential pathogenic bacteria triggered when the cell loses its integrity. Further, this pathway may act against multiple threats to the microalga, including grazers, as fatty acids exhibit activity in diverse biological assays. Finally, whilst two of the fatty acids, (9Z)-hexadecenoic acid and (5Z, 8Z, 11Z, 14Z, 17Z)-eicosapentaenoic acid, inhibited the growth of MRSA their usefulness as therapeutic compounds may be limited due to their instability and their broad biological activity.
119

Mechanism of anti-influenza virus activity of Maillard reaction products derived from Isatidis roots

Ke, Lijing January 2011 (has links)
The cyto-protective compositions and effects of antiviral Maillard reaction products (MRPs) derived from roots of Isatis indigotica F. were examined using biochemical and biophysical methods. The Maillard reaction was identified as the main source of compounds with antiviral activity, an observation which has led to the proposal of a new class of active compounds that protect cells from influenza virus infection. In the roots, arginine and glucose were revealed to be the predominant reactants for the Maillard reaction. Significant anti-influenza virus effects were demonstrated in the RIE MRPs derived from the roots (RIE refers to the ‘radix Isatidis extracts’), and in Arg-Glc MRPs which are synthesised with arginine and glucose. Arg-Glc MRPs were confirmed as suitable models for the study of the antiviral effects of the root extracts. Furthermore, RIE MRPs and Arg-Glc MRPs were found to bind to the plasma membranes of erythrocytes and MDCK cells, and altered their properties. A novel antiviral mechanism was proposed: that MRPs achieve their cyto-protective effects by binding to the cell membrane rather than by direct action on viral particles. To validate the proposed mechanism, the interaction between MRPs and membrane lipids was investigated by biophysical experiments with phospholipids bilayers. Arg-Glc MRPs affected the rigidity of lipid packing in monolayers and bilayers, while RIE MRPs enhanced the fluidity. Both types of MRPs inserted into the hydrophobic core of bilayers, to differing extents, and induced the stabilisation or destabilisation of bilayers in a concentrationdependent manner. At certain concentrations, MRPs prevented the lamellar structure of bilayers from being destabilised by a viral fusion peptide, improved the lipid order and thereby inhibited cell-virus membrane fusion. The mechanism of the anti-influenza virus activity of RIE was therefore correlated to the interaction between MRPs and phospholipid bilayers, an integral component of the plasma membrane.
120

Potentiel antimicrobien de principes actifs d’origine naturelle / Antimicrobial potential of natural bioactive compounds

Johansen, Bianca 22 December 2017 (has links)
Le développement de principe actif à partir de ressources naturelles pourrait être un moyen pour développer de nouvelles alternatives aux antibiotiques. L’huile essentielle d’arbre à thé est reconnue pour ses nombreuses propriétés et son activité antimicrobienne à spectre large, mais aussi pour sa toxicité et sa forte teneur en allergènes liée à sa composition en monoterpènes. Dans cette étude, nous cherchons de nouveaux principes actifs naturels issus de l’huile essentielle d’arbre à thé, qui auraient une activité antimicrobienne équivalente mais une toxicité et un pouvoir allergène réduit. Deux principes actifs ont ainsi été étudiés au cours de ce travail. Le Titroléane™, qui est une fraction de l’huile essentielle d’arbre à thé enrichi en monoterpène alcools mais avec un très faible taux de monoterpène, a montré des activités microbiologiques similaires à l’huile essentielle d’arbre à thé. La Synterpicine™ quant à elle, est uniquement composée des deux molécules majoritaires de l’huile essentielle, et présente une cytotoxicité réduite. La caractérisation de l’activité des principes actifs a été menée avec différentes méthodes d’études in vitro, pour définir leur activité inhibitrice et bactéricide, sur des bactéries planctoniques et en biofilm. Enfin, la recherche de nouvelles molécules actives au sein des principes actifs, s’est poursuivie à l’aide d’une méthode de chromatographie sur couche mince haute performance, couplée à une étude d’activité microbiologique par bioautographie. Cette étude a mis en évidence l’activité antimicrobienne de deux nouveaux principes actifs d’origine naturelle, pouvant être valorisés sur différents marchés notamment la santé humaine / The development of a natural bioactive compounds could be a mean of developing new alternatives to antibiotics. Tea tree essential oil is known for its numerous properties and its broad-spectrum antimicrobial activity, but also for its toxicity and its high content in allergens due to its composition in monoterpenes. In this study, we search for new natural compounds extracted from tea tree essential oil, which has equivalent antimicrobial activity but less toxicity and a reduced allergenic activity. Two bioactive compounds have been thus studied. Titroléane™ - a fraction of tea tree essential oil enriched in monoterpene alcohols but with a very low rate of monoterpenes - has shown microbiological activities similar to tea tree essential oil. As for Synterpicine™, it is only composed of the two main molecules of the essential oil, and presents a reduced cytotoxicity. The characterization of the compounds’ efficacy was carried out with different in vitro study methods, to define their inhibitory and bactericide activity, on planktonic and biofilm bacteria. Finally, the research of new active molecules within the active compounds, was pursued thanks to a high performance thin layer chromatography, paired up with a microbiological study by bioautography. This study has highlighted the antimicrobial activity of two new natural active extracts which can be valorised on different markets- especially human health

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