This thesis describes phytochemical studies on two medically important plants, Buxus natalensis and Drypetes gossweileri. Chemical investigation on the acetylcholinesterase inhibiting chloroform extracts, obtained at pH 7.0 and 9.5 resulted in the isolation of seven natural products: O10-natafuranamine (123), cyclonataminol A (124), 31-demethylbuxaminol A (125), buxaminol A (126), buxaminol C (127), p coumaroylputrescine (128) and methyl syringate (129). Compound 123 is a member of a rarely occurring class of Buxus alkaloids containing a tetrahydrofuran ring incorporated in its structure. Compounds 123-129 were isolated for the first time from this plant. Structures of compounds 123-129 were elucidated with the aid of NMR and MS spectral data. All of these isolates exhibited different levels of AChE inhibitory activities with compound 123 being significantly active in this bioassay with an IC50 of 8.5 µM compared to the rest of the isolates. Compounds 123-129 were inactive in antimicrobial assays. Phytochemical studies on the crude extract of Drypetes gossweileri resulted in the isolation of a new N-linked aromatic glycoside, N-β-glucopyranosyl-p-hydroxy phenyl acetamide (151), along with two known compounds, p-hydroxy phenyl acetic acid (152) and p hydroxyphenyl acetonitrile (153). Compounds 151-153 exhibited moderate to weak AChE inhibitory activities.

This thesis describes phytochemical studies on two medically important plants, Buxus natalensis and Drypetes gossweileri. Chemical investigation on the acetylcholinesterase inhibiting chloroform extracts, obtained at pH 7.0 and 9.5 resulted in the isolation of seven natural products: O10-natafuranamine (123), cyclonataminol A (124), 31-demethylbuxaminol A (125), buxaminol A (126), buxaminol C (127), p coumaroylputrescine (128) and methyl syringate (129). Compound 123 is a member of a rarely occurring class of Buxus alkaloids containing a tetrahydrofuran ring incorporated in its structure. Compounds 123-129 were isolated for the first time from this plant. Structures of compounds 123-129 were elucidated with the aid of NMR and MS spectral data. All of these isolates exhibited different levels of AChE inhibitory activities with compound 123 being significantly active in this bioassay with an IC50 of 8.5 µM compared to the rest of the isolates. Compounds 123-129 were inactive in antimicrobial assays. Phytochemical studies on the crude extract of Drypetes gossweileri resulted in the isolation of a new N-linked aromatic glycoside, N-β-glucopyranosyl-p-hydroxy phenyl acetamide (151), along with two known compounds, p-hydroxy phenyl acetic acid (152) and p hydroxyphenyl acetonitrile (153). Compounds 151-153 exhibited moderate to weak AChE inhibitory activities.

<p> Pramanicin (1) is a natural product that was first isolated as an anti-fungal agent: it possesses bioactivity against both the acapsular and capsular forms of Cryptococcus neoformans. 1 was found to act on smooth muscle in an endotheliumdependent manner. Further, studies of Ca2+ release from the endoplasmic reticulum of endothelial cells were consistent with an influence on the endothelial nitric oxide synthase (eNOS) pathway. Recently, we showed that 1 activates caspases 3 and 9. In order to determine which functional groups in 1 are required for this activity, several analogues were prepared (2~7). These included 2 and 3 prepared through fermentation and modification of 1, as well as 4-7 which were prepared by chemical synthesis. A test of bioactivity for 1-7 indicates that all compounds are active. The small differences in activity are discussed. </p> / Thesis / Master of Science (MSc)

No description available.

No description available.

No description available.

Seaweed has traditionally been used in Scotland and other countries both as food and for medicinal purposes, which has led to seaweed being investigated for their natural product content. Despite over 30 years of research, the majority of species found in Scotland have yet to have their chemistry examined. Extracts of seaweed were tested for antimicrobial activity against marine bacteria. Extracts of Palmaria palmata, Ulva linza, Chondrus crispus and Pelvetia canaliculata showed no detectable activity, while ethyl acetate extracts of Fucus serratus, Halidrys siliquosa, Osmundea pinnatifida and Polysiphonia fucoides showed activity against at least six of the seven strains. Extracts were screened for radical scavenging activity against ABTS, DPPH and superoxide radicals. At least one extract from each brown seaweed showed radical scavenging of at least 80 % towards ABTS+ with an ethyl acetate extract of P. fucoides and H siliquosa quenching DPPH by at least 90%. Radical scavenging activity appears to be dependent total phenolic content of extract. Extracts were subjected to a series of assays relevant to human health. Ethyl acetate extracts showed high antiparasitic activity against Trypanosoma brucei with a P. fucoides extract showing antibacterial activity toward Staphylococcus aureus. Extracts of H siliquosa and F. serratus showed cytotoxicity to Hela cells with extracts of H siliquosa showing cytotoxicity to LN CAP AS and PC 3 cell lines. An extract of H siliquosa underwent chromatography and by applying assay guided fractionation, several active fractions were identified. These were analysed using NMR and LC/MS and four compounds identified: (2E. 6E. 14E)-1-(l'-hydroxy-4'-methoxy-6'-methyl- phenyl)-5, 13-dihydroxy-12-one-3, 7, 11, 15-tetramethylhexadeca-2, 6, 14-triene, a known antibacterial compound, previously identified in H siliquosa; (2E, 6E, 10E, l4E)-1-(1'- hydroxy-4'-methoxy-6'-methyl phenyl)-5, 12 dihydroxy-3.7, 11, 15-tetramethyl hexadeca- 2.6, 10, l4-tetraene, previously identified in Cystoseira elegans, and now in H siliquosa; and two compounds that have not been reported before.

L'hydroxapatite (HA) est largement utilisée comme matériau de revêtement pour l'implant de la hanche en raison de sa bioactivité exceptionnelle. Il est également flexible et peut accueillir des ions dans sa structure. Le zinc (Zn) est un bon ion dopant comme il stimule la formation osseuse et présente des caractéristiques antibactériennes utiles qui peuvent aider à lutter contre les infections chirurgicales. Les implants de hanche revêtus d‟HA sont classiquement préparés par pulvérisation par plasma en poudre. Un processus émergent appelé projection de plasma de précurseur de solution (SPPS) est intéressant car il permet le dépôt de revêtements ayant des caractéristiques nanométriques/submicrométriques. Ce travail de recherche porte sur la fabrication de revêtements d‟HA et HA dopés Zn par SPPS. L'influence des précurseurs de solution de départ et des paramètres opérationnels du processus de projection sur les caractéristiques microstructurales d‟HA est discutée. Les mécanismes de croissance des revêtements obtenus en utilisant différents séries de précurseurs sont présentés. En outre, différents modèles sont utilisés pour décrire les propriétés mécaniques des revêtements HA par SPPS et sont corrélés à leurs microstructures. Le mécanisme de dopage en Zn à d‟HA par SPPS et son rôle pour inhiber la formation d'HA sont démontrés. Enfin, la comportement in vitro sous fluide corporel simulé (SBF) est présentée. On forme une couche d'apatite de type osseux sur la surface du revêtement HA, mais l'expérience a validé l'effet inhibiteur du Zn sur la formation d‟apatite. / Hydroxyapatite (HA) is widely used as coating material for hip implant due to its exceptional bioactivity. It is also flexible and can accommodate ions into its structure. Zinc (Zn) is a good dopant ion as it stimulates bone formation and exhibits useful antibacterial characteristics which can help fight surgical infections. HA-coated hip implants are conventionally prepared by powder plasma spraying process. An emerging process called solution precursor plasma spraying (SPPS) is an interesting one as it allows for the deposition of coatings having nanometric/ submicrometric features. This research work presents about the fabrication of HA and Zn doped HA coatings by SPPS. The influence of starting solution precursors and operational spray process parameters to the microstructural characteristics of HA is discussed. The coating build-up mechanisms of the obtained coatings using different sets of precursors are presented. Moreover, different models are used to describe the mechanical properties of the SPPS HA coatings and are correlated to their microstructures. Mechanism of Zn doping to HA by SPPS and its role for inhibiting HA formationare demonstrated. Finally, the in-vitro behaviour under simulated body fluid (SBF) is presented. Bone-like apatite layer on HA coating‟s surface is formed but the experiment validated the inhibiting effect of Zn to apatite formation.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20234号 / 医博第4193号 / 新制||医||1019(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 安達 泰治, 教授 横出 正之, 教授 鈴木 茂彦 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Cannabis sativa has a complex history of classification and traditional use. Cannabis sativa ssp. sativa and spp. indica are the two major lineages of cannabis and, through artificial selection, many strains or cultivars are found within each group are bred together to yield hybrid plants. New methods of classification based on Δ⁹-Tetrahydrocannbinol (THC) and Cannabidiol (CBD) content as well as minor cannabinoids and terpenes have emerged as a more effective classification of cannabis. However, the fidelity of cannabis varieties relative to their respective strain names and lineages (indica, sativa and hybrid) based on chemistry has been brought into question. THC and more recently CBD are collectively responsible for the psychoactive and therapeutic effects of cannabis and minor cannabinoids and terpenes are emerging as having their own unique bioactivity or synergistic effects in vitro. Considering the variation in cannabis chemical profile and infidelity to strain names or lineages, we investigated the cannabinoid, terpene and metabolomic profiles of 33 THC-dominant strains (113 samples) to evaluate existing and alternative chemistry-based classification systems using multivariate analyses. Here, we conclude that Indica-Sativa-Hybrid designations are insufficient in describing variation in cannabinoid, terpene and metabolomic data, and that a terpene-based profile classification revealed robust groupings in cannabinoid-terpene data. However, terpene profiles were not discernable in metabolomic data. To investigate how chemical complexity and variability impacts bioactivity, we compared the activity of cannabis extracts to that of pure THC (and CBD) to determine if THC alone is driving activity. THC, CBD, and plant extracts were tested in vitro for cytotoxicity in BEAS-2Bs cells and for cannabinoid receptor signalling activity using a human CB₁-HEK293 cell model. THC did not completely dictate 24-hour toxicity in BEAS-2B cells suggesting that other extract components (beyond THC and CBD) are contributing to cytotoxicity. While CBD alone was 2x more toxic than THC alone, THC:CBD do no predict toxic concentration. THC within extracts appeared to drive efficacy at CB₁ receptors by reducing intracellular cAMP accumulation but did not dictate variation in EC₅₀. THC in extract also appeared to increase percent cAMP reduction in cells regardless of low CBD content but a 1:1 balanced THC/CBD extract revealed reduced percent cAMP reduction. Pure compounds compared to extracts of the same THC/CBD ratio performed very similarly at CB1 receptors besides 1:1 extract preparation having reduced % reduction of cAMP compared to 1:1 pure compounds suggestive of NAM by extract components. Regression modelling of THC within extract revealed a significant positive relationship in % cAMP reduction (Emax) but no significance in TC₅₀ and EC₅₀. This work demonstrates the importance of rigorous analysis of cannabis chemistry as well as evaluation of extracts in bioactivity assays.