Thesis (M.S.)--Oregon State University, 2000. / Typescript (photocopy). Includes mounted photographs. Includes bibliographical references (leaves 76-81). Also available on the World Wide Web.

M.Tech.

Doctor Educationis / It is believed that early humans had knowledge of how to use traditional medicinal plants, but the knowledge has been partially lost as society underwent various changes leading to new civilizations. The aim of this study was to isolate and identify natural product constituents from Tulbaghia Alliacea. There has not yet been any scientifically conducted investigation on the plant. Tulbaghia Alliacea is used for fever and colds, asthma, pulmonary tuberculosis and stomach problems. / South Africa

No description available.

Magister Pharmaceuticae - MPharm / An aqueous extract prepared from the leaves and smaller stems of Leonotis leonorus was used to investigate the potential effects on certain cardiovascular parameters such as left ventricular systonic pressure, end-diastolic pressure, developed pressure, heart rate, cardiac work and coronary perfusion pressure in isolated rat hearts. / South Africa

Magister Pharmaceuticae - MPharm / The specific objectives of this study were to investigate whether Artemisia Afra, Leonotis leonorous and Mentha Longiflora have PDE 4 inhibitory activity, to determine and compare the levels of the total phenolic compunds , total and individual flavanoids, especially luteolin and hesperetin, in the three plants and finally, to determine if there was a correlation between the PDE inhibitory activity and the levels of flavanoids or phenolic compounds in the plants. It was hypothesized that the plants with higher levels of total flavonoid and/or aglycone luteolin and/or hesperetin had higher PDE inhibitory activity. / South Africa

Plants have always been a source of medicine and are still being used by traditional healers in the rural part of Africa, Asia and India to treat a range of illnesses including cancer. The in vitro anticancer activity of an 80 percent ethanol extract of Cyathula prostrata, an annual branching shrub used by traditional healers in Nigeria to treat cancer was investigated. No previous studies have outlined the possible pathways and mechanisms used by cancer cells when treated with C. prostrata. Dose response analysis was performed to determine the effective cytotoxic concentrations of C. prostrata on HeLa (cervical cancer cell line) and U937 (myelo-monocytic cell line). The IC50 values were 100.8 μg/ml and 64.4 μg/ml for HeLa and U937 cells, respectively. All further experiments were performed using 125 μg/ml C. prostrata extract and 50 μM cisplatin as positive control. With the use of the fluorescent DNA binding dye propidium iodide, the induction of tumour cell death by C. prostrata extract has been linked to cell cycle arrest in the G1 phase at 24 and 48 h. In both cell lines, more than 80 percent of the C. prostrata treated cells were found in the G1 phase after 48 hours of treatment. The annexin V-FITC/PI assay revealed an increase in the percentage apoptotic cells from 4.9 percent to 53.1 percent at 24 h and 8.3 percent to 50.3 percent at 48 h. Since apoptosis induction can occur via a number of different pathways, distinct features were used as markers to investigate the mode of action of this C. prostrata extract. Markers such as activated caspase-8, p21 and cyt-c, were investigated with the aid of fluorescently labelled (FITC) antibodies with analysis using flow cytometry. No change in p21 levels was observed in response to treatment with the extract for up to 48 h. Cell cycle arrest in G1 was therefore not induced by this cyclin-CDK inhibitor. Increase in caspase-8 activation was observed in response to treatment with the extract with no cyt-c release from the mitochondria. The lack of cyt-c release was due to no change in mitochondrial membrane potential, which was investigated with the aid of fluorescent mitochondrial dyes and flow cytometric techniques. Caspase-8 activation is unique to the extrinsic apoptotic pathway. The results from this study therefore show that C. prostrata extract induces apoptosis via the extrinsic pathway and that this activation in independent of the mitochondria. The levels of hTERT, the catalytic subunit of telomerase, were investigated as an additional molecular target for C. prostrata. This was also investigated using FITC labelled antibodies and flow cytometry. A decrease in hTERT levels was observed following C. prostrata treatment. The findings from this study suggest that the extract acts through multiple targets, by inducing: cell cycle arrest in the G1 phase through an unknown mechanism; apoptosis through an extrinsic death receptor pathway and replicative senescence through inhibition of telomerase.

Cancer is the second biggest global killer,[1,2] with cancers of the brain and central nervous system accounting for a disproportionately high number of deaths.[3] The most prolific cancer of the central nervous system is glioblastoma, for which prognosis is still very poor. In this project, analogues of two lead compounds with known activity against glioblastoma cell lines (compounds 4 and 5, Figure 1) were produced in order to develop structure-activity relationships and discover compounds with superior activities against glioblastoma. Figure 1 - The structures of the lead compounds 4 and 5 Analogues of compound 4 were the result of a rigorous similarity search of the ZINC database,[4,5] as well as using chemical intuition to identify potential analogues. A scaffold-hopping approach was undertaken, through which two new compound classes were identified as potentially superior lead compounds for future work (Figure 2). Figure 2 - The structures of two analogues of compound 4 with different scaffolds and superior activity, compounds 168 and 214 Compound 4 is known to induce cell death through the induction of elevated levels of cellular reactive oxygen species (ROS),[6] which may be formed via the radical form of compound 4 and its analogues. The connection between the anticancer activity of 4 and its analogues with the propensity of these compounds to form radicals was also investigated. Enthalpic values relevant to radical formation (BDE, AIP, PDE, PA and ETE) were calculated using a density functional theory (DFT) approach. Although no strong correlation was found for the whole series of compounds, the data indicates that correlations may exist within certain structural classes. The anticancer activity of compound 5, a prodrug, was compared against 11 analogues of both the prodrug and active form of the compound (Scheme 1). It was found that compound 9 has superior activity to that of the prodrug 5. Substitutions at the N-position of 5 were also found to have a significant effect on activity, with an N-tosyl analogue having significantly improved activity against glioblastoma cell lines and short term cultures. The results obtained suggest that future work on this series should therefore be based around compound 9, a subclass of indoles that have wide ranging anticancer activity, but have not yet been reported against glioblastoma. Scheme 1 - The degradation of 5 into its suspected active form (9) In conclusion, analogues were discovered within this project which improved upon the anticancer activity of both compounds 4 and 5. For compound 4, two alternative scaffolds were identified as superior and novel lead compounds against glioblastoma, and there is some indication that there may be a correlation between radical formation and anticancer activity within specific structural classes of this functional class of compounds. For prodrug 5, substituents at the N positon were found to have a significant effect on activity, and the activity of the active form (9) was found to be superior to the activity of the prodrug.

No description available.

Wong Man-po. / Thesis (M. Phil.)--Chinese University of Hong Kong, 1980. / Bibliography: leaves 88-91.